Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 19 de 19
Filter
1.
Article in Chinese | WPRIM | ID: wpr-879024

ABSTRACT

The aim of this paper was to study the protective effect of total flavonoids from Rosa multiflora(TF-RM) on the injury of HUVEC induced by oxidized low density lipoprotein(ox-LDL). SPF male SD rats were randomly divided into blank group, simvastatin group(1.8 mg·kg~(-1)·d~(-1)) and TF-RM group(2.5 g·kg~(-1)·d~(-1)), with 10 rats in each group. They were intragastrically administered with drugs for 7 days, and then blood was collected from the abdominal aorta to prepare drug-containing serum. The HUVEC injury model was established through ox-LDL induction, and added with 15% simvastatin, 5% TF-RM, 10% TF-RM, 15% TF-RM drug-containing serum and blank serum, respectively. Reactive oxygen species(ROS) was determined by flow cytometry. Nitric oxide(NO) content was determined by nitrate reductase method. The contents of ET-1, P-selectin, E-selectin, ICAM-1, VCAM-1, IL-1β, IL-6 and TNF-α were determined by ELISA. The expression of Lox-1 protein was determined by Western blot. Compared with the blank group, ROS level in HUVEC and the contents of ET-1, P-selectin, E-selectin, ICAM-1, VCAM-1 and IL-1β in HUVEC were significantly increased(P<0.05), NO decreased significantly(P<0.01),Lox-1 protein expression increased significantly(P<0.05), and TNF-α and IL-6 showed an increasing trend. Compared with the model group, TF-RM significantly reduced ROS level in HUVEC and ET-1, P-selectin, E-selectin, ICAM-1, TNF-α, IL-1β content in supernatant(P<0.05), significantly increased NO content(P<0.01), and inhibited Lox-1 protein expression(P<0.05). VCAM-1, IL-6 contents showed a decreasing trend. Serum containing TF-RM acts on lectin-like oxidized low-density lipoprotein receptors, and exerts a protective effect on vascular endothelial cells by reducing cell oxidative damage, regulating vasoactive substances, and reducing adhesion molecules and inflammatory cascades.


Subject(s)
Animals , Cells, Cultured , Endothelial Cells , Endothelium, Vascular , Flavonoids/pharmacology , Intercellular Adhesion Molecule-1/genetics , Lipoproteins, LDL , Male , Rats , Rats, Sprague-Dawley , Rosa
2.
Article in Chinese | WPRIM | ID: wpr-878793

ABSTRACT

The aim of this paper was to investigate the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in mice with delayed hypersensitivity and explore its possible mechanism. The delayed-type hypersensitivity(DTH) model in mice was established to observe the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in DTH mice. ELISA assay was used to detect the contents of interferon(IFN-γ); histopathological changes and degree of mononuclear infiltration of right ear tissues were examined by HE staining; the expression level of intercellular cell adhesion molecule-1(ICAM-1) in the right ear of mice was detected by immunohistochemistry; the protein expression levels of p38 phospho mitogen activated protein kinase(p-p38 MAPK) was detected by Western blot analysis. As compared with the control group, the degree of ear swelling, thymus/spleen index, serum IFN-γ as well as the number and degree of infiltration of monocytes were significantly increased in the model group. As compared with the model group, the degree of ear swelling and thymus/spleen index of the mice in the combination group were significantly reduced; the number and degree of infiltration of monocytes were significantly relieved; the serum levels of IFN-γ and the expression levels of p-p38 MAPK and ICAM-1 proteins in the right ear were also significantly reduced. The combination of dihydroartemisinin and Huobahua can significantly inhibit the DTH response, and it may regulate the production and secretion of related inflammatory factor IFN-γ by inhibiting the phosphorylation activity of p38 MAPK, thereby further reducing the expression of ICAM-1 and thus exerting the immunosuppressive effect.


Subject(s)
Animals , Artemisinins , Intercellular Adhesion Molecule-1/genetics , Mice , Monocytes , p38 Mitogen-Activated Protein Kinases/genetics
3.
Arq. bras. cardiol ; 104(6): 476-485, 06/2015. tab, graf
Article in English | LILACS | ID: lil-750695

ABSTRACT

Background: Circulatory power (CP) and ventilatory power (VP) are indices that have been used for the clinical evaluation of patients with heart failure; however, no study has evaluated these indices in patients with coronary artery disease (CAD) without heart failure. Objective: To characterize both indices in patients with CAD compared with healthy controls. Methods: Eighty-seven men [CAD group = 42 subjects and healthy control group (CG) = 45 subjects] aged 40–65 years were included. Cardiopulmonary exercise testing was performed on a treadmill and the following parameters were measured: 1) peak oxygen consumption (VO2), 2) peak heart rate (HR), 3) peak blood pressure (BP), 4) peak rate-pressure product (peak systolic HR x peak BP), 5) peak oxygen pulse (peak VO2/peak HR), 6) oxygen uptake efficiency (OUES), 7) carbon dioxide production efficiency (minute ventilation/carbon dioxide production slope), 8) CP (peak VO2 x peak systolic BP) and 9) VP (peak systolic BP/carbon dioxide production efficiency). Results: The CAD group had significantly lower values for peak VO2 (p < 0.001), peak HR (p < 0.001), peak systolic BP (p < 0.001), peak rate-pressure product (p < 0.001), peak oxygen pulse (p = 0.008), OUES (p < 0.001), CP (p < 0.001), and VP (p < 0.001) and significantly higher values for peak diastolic BP (p = 0.004) and carbon dioxide production efficiency (p < 0.001) compared with CG. Stepwise regression analysis showed that CP was influenced by group (R2 = 0.44, p < 0.001) and VP was influenced by both group and number of vessels with stenosis after treatment (interaction effects: R2 = 0.46, p < 0.001). Conclusion: The indices CP and VP were lower in men with CAD than healthy controls. .


Fundamento: Os índices da Potência Circulatória (PC) e Potência Ventilatória (PV) têm sido utilizados para avaliação clínica de pacientes com insuficiência cardíaca, mas nenhum estudo avaliou esses índices em pacientes com Doença Arterial Coronariana (DAC). Objetivo: Caracterizar ambos os índices em pacientes com DAC comparados a indivíduos saudáveis. Métodos: Oitenta e sete homens [grupo DAC = 42 sujeitos e, grupo controle (GC) = 45 sujeitos] com idade entre 45 e 65 anos foram incluídos. Um Teste de Exercício Cardiopulmonar (TECP) foi realizado em esteira e as seguintes variáveis foram obtidas: 1) consumo de oxigênio (VO2) pico; 2) Frequência Cardíaca (FC) pico; 3) Pressão Arterial (PA) pico; 4) duplo produto pico (PA sistólica pico x FC pico); 5) pulso de oxigênio pico (VO2 pico dividido pela FC pico); 6) eficiência ventilatória para o consumo de oxigênio (OUES); 7) eficiência ventilatória para a produção de dióxido de carbono (VE/VCO2 slope); 8) PC (VO2 pico x PA sistólica pico); e 9) PV (PA sistólica pico dividido pelo VE/VCO2 slope). Resultados: O grupo DAC apresentou valores significativamente menores das seguintes variáveis no pico do exercício: VO2 (p < 0,001), FC (p < 0,001), PA sistólica (p < 0,001), duplo produto (p < 0,001), pulso de oxigênio (p = 0,008), OUES (p < 0,001), PC (p < 0,001) e PV (p < 0,001), e valores significativamente maiores de PA diastólica (p = 0,004) e VE/VCO2 slope (p < 0,001) em relação ao GC. Uma análise de regressão pelo método stepwise mostrou que a PC foi influenciada pelo grupo (R2 = 0,44, p < 0,001) e a PV tanto pelo grupo quanto pelo número de vasos com estenose pós tratamento (efeito de interação: R2 = 0,46, p < 0,001). Conclusion: Os índices da PC e PV foram menores em homens com DAC comparados ao GC, podendo dessa forma ser utilizados na caracterização dessa população. .


Subject(s)
Animals , Humans , Aluminum Oxide/toxicity , Cell Adhesion Molecules/metabolism , Cell Adhesion/drug effects , Endothelium, Vascular/drug effects , Metal Nanoparticles/toxicity , Cells, Cultured , Cell Adhesion Molecules/genetics , Dose-Response Relationship, Drug , E-Selectin/genetics , E-Selectin/metabolism , Endothelium, Vascular/metabolism , Endothelium, Vascular/ultrastructure , Gene Expression/drug effects , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , Microscopy, Electron, Transmission/methods , Monocytes/drug effects , Monocytes/metabolism , Monocytes/ultrastructure , Particle Size , RNA, Messenger/metabolism , Swine , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/metabolism
4.
Article in English | WPRIM | ID: wpr-159658

ABSTRACT

The acquisition of metastasis potential is a critical point for malignant tumors. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a potential tumor suppress gene and frequently down-regulated in malignant tumors. It has been implicated that overexpression of MDA-7 led to proliferation inhibition in many types of human tumor. Invasion is an important process which is potential to promote tumor metastasis. However, the role and potential molecular mechanism of mda-7/IL-24 to inhibit the invasion of human melanoma cancer is not fully clear. In this report, we identified a solid role for mda-7/IL-24 in invasion inhibition of human melanoma cancer LiBr cells, including decreasing of adhesion and invasion in vitro, blocking cell cycle, down-regulating the expression of ICAM-1, MMP-2/9, CDK1, the phosphorylation of ERK and Akt, NF-kappaB and AP-1 transcription activity. Meanwhile, there was an increased expression of PTEN in mda-7/IL-24 over-expression LiBr cells. Our results demonstrated that mda-7/IL-24 is a potential invasion suppress gene, which inhibits the invasion of LiBr cells by the down-regulation of ICAM-1, MMP-2/9, PTEN, and CDK1 expression. The molecular pathways involved were the MAPK/ERK, PI3K-Akt, NF-kappaB, and AP-1. These findings suggest that mda-7/IL-24 may be used as a possible therapeutic strategy for human melanoma cancer.


Subject(s)
CDC2 Protein Kinase/genetics , Cell Line, Tumor , Cell Movement , Down-Regulation , G2 Phase Cell Cycle Checkpoints , Humans , Intercellular Adhesion Molecule-1/genetics , Interleukins/genetics , M Phase Cell Cycle Checkpoints , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Melanoma/metabolism , NF-kappa B/genetics , PTEN Phosphohydrolase/genetics , Phosphorylation , Proto-Oncogene Proteins c-akt/genetics , Transcription Factor AP-1/genetics , Up-Regulation
5.
Article in English | WPRIM | ID: wpr-223717

ABSTRACT

Behcet's disease (BD) is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent uveitis, oral and genital ulcers and skin lesions. To identify some pathogenic variants associated with severe Behcet's uveitis, we used targeted and massively parallel sequencing methods to explore the genetic diversity of target regions. A solution-based target enrichment kit was designed to capture whole-exonic regions of 132 candidate genes. Using a multiplexing strategy, 32 samples from patients with a severe type of Behcet's uveitis were sequenced with a Genome Analyzer IIx. We compared the frequency of each variant with that of 59 normal Korean controls, and selected five rare and eight common single-nucleotide variants as the candidates for a replication study. The selected variants were genotyped in 61 cases and 320 controls and, as a result, two rare and seven common variants showed significant associations with severe Behcet's uveitis (P<0.05). Some of these, including rs199955684 in KIR3DL3, rs1801133 in MTHFR, rs1051790 in MICA and rs1051456 in KIR2DL4, were predicted to be damaging by either the PolyPhen-2 or SIFT prediction program. Variants on FCGR3A (rs396991) and ICAM1 (rs5498) have been previously reported as susceptibility loci of this disease, and those on IFNAR1, MTFHR and MICA also replicated the previous reports at the gene level. The KIR3DL3 and KIR2DL4 genes are novel susceptibility genes that have not been reported in association with BD. In conclusion, this study showed that target enrichment and next-generation sequencing technologies can provide valuable information on the genetic predisposition for Behcet's uveitis.


Subject(s)
Adult , Aged , Behcet Syndrome/genetics , Case-Control Studies , Female , Histocompatibility Antigens Class I/genetics , Humans , Intercellular Adhesion Molecule-1/genetics , Interferon-alpha/genetics , Male , Middle Aged , Polymorphism, Single Nucleotide , Receptors, IgG/genetics , Receptors, KIR/genetics , Receptors, KIR2DL4/genetics
6.
Acta cir. bras ; 27(9): 645-649, Sept. 2012. ilus
Article in English | LILACS | ID: lil-646732

ABSTRACT

PURPOSE: To compare gene expression of the chemokines RANTES and eotaxin-2, its receptor, CCR-3, adhesion molecule ICAM-1 and its receptor LFA-1 in eosinophilic polyps and in control normal nasal mucosa. METHODS: Gene expression was quantified by Real Time PCR in polyps (n=35) and in healthy nasal mucosa (n=15). RESULTS: Eosinophilic polyps showed a higher expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa. CONCLUSION: Eosinophilic polyps present greater expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa.


OBJETIVO: Comparar a expressão gênica das quimiocinas RANTES e eotaxina-2, do seu receptor CCR-3, da molécula de adesão ICAM-1 e do seu receptor LFA-1 entre pólipos nasais eosinofílicos (PE) (n=35) e mucosa nasal controle (n=15). MÉTODOS: Quantificou-se a expressão gênica dos mediadores citados pela técnica de PCR em tempo real em PEs e em mucosas de concha média de pacientes sem doenças nasais ou alteração endoscópica. RESULTADOS: Pólipos eosinofílicos apresentam maior expressão de eotaxina-2 e RANTES, mas não de CCR-3, ICAM-1 e LFA-1, quando comparados as mucosas nasais controles. CONCLUSÃO: Pólipos eosinofícios apresentaram maior expressão de eotaxin-2 and RANTES, mas não de CCR-3, ICAM-1 ou LFA-1,comparada à mucosa nasal controle.


Subject(s)
Humans , Nasal Polyps/metabolism , Rhinitis/metabolism , Sinusitis/metabolism , Case-Control Studies , Chronic Disease , /genetics , /metabolism , /genetics , /metabolism , Gene Expression , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , Lymphocyte Function-Associated Antigen-1/genetics , Lymphocyte Function-Associated Antigen-1/metabolism , Nasal Mucosa , Nasal Polyps/complications , Polymerase Chain Reaction , /genetics , /metabolism , Rhinitis/complications , Sinusitis/complications
7.
Yonsei Medical Journal ; : 1165-1175, 2012.
Article in English | WPRIM | ID: wpr-183497

ABSTRACT

PURPOSE: This study was undertaken to investigate the effects of gamma linolenic acid (GLA) on inflammation and extracellular matrix (ECM) synthesis in mesangial and tubular epithelial cells under diabetic conditions. MATERIALS AND METHODS: Sprague-Dawley rats were intraperitoneally injected with either a diluent [n=16, control (C)] or streptozotocin [n=16, diabetes (DM)], and eight rats each from the control and diabetic groups were treated with evening primrose oil by gavage for three months. Rat mesangial cells and NRK-52E cells were exposed to medium containing 5.6 mM glucose and 30 mM glucose (HG), with or without GLA (10 or 100 microM). Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and fibronectin (FN) mRNA and protein expression levels were evaluated. RESULTS: Twenty-four-hour urinary albumin excretion was significantly increased in DM compared to C rats, and GLA treatment significantly reduced albuminuria in DM rats. ICAM-1, MCP-1, FN mRNA and protein expression levels were significantly higher in DM than in C kidneys, and these increases were significantly abrogated by GLA treatment. In vitro, GLA significantly inhibited increases in MCP-1 mRNA expression and protein levels under high glucose conditions in HG-stimulated mesangial and tubular epithelial cells (p<0.05, respectively). ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. CONCLUSION: GLA attenuates not only inflammation by inhibiting enhanced MCP-1 and ICAM-1 expression, but also ECM accumulation in diabetic nephropathy.


Subject(s)
Animals , Anti-Inflammatory Agents/therapeutic use , Blotting, Western , Chemokine CCL2/genetics , Diabetic Nephropathies/drug therapy , Enzyme-Linked Immunosorbent Assay , Fibronectins/genetics , Intercellular Adhesion Molecule-1/genetics , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , alpha-Linolenic Acid/therapeutic use
8.
Article in English | WPRIM | ID: wpr-119896

ABSTRACT

We previously demonstrated that there are acute and delayed phases of renal protection against renal ischemia and reperfusion (IR) injury with renal ischemic preconditioning (IPC). This study assessed whether hepatic IPC could also reduce distant renal IR injury through the blood stream-mediated supply of reactive oxygen species (ROS). Male C57BL/6 mice were randomly divided into four groups: group I, sham operated including right nephrectomy; group II (IR), left renal ischemia for 30 min and reperfusion injury; group III (IPC-IR), hepatic ischemia for 10 min followed by 10 min of reperfusion before left renal IR injury; group IV (MPG - IPC + IR), pretreated with 100 mg/kg N-(2-mercaptopropionyl)-glycine (MPG) 15 min before hepatic IPC and left renal IR injury. Renal function, histopathologic findings, proinflammatory cytokines, and cytoprotective proteins were evaluated 15 min or 24 hr after reperfusion. Hepatic IPC attenuated the expression of proinflammatory cytokines, tumor necrosis factor alpha, intercellular adhesion molecule 1, and induced inducible nitric-oxide synthase, and the phosphorylation of Akt in the murine kidney. Renal function was better preserved in mice with hepatic IPC (group III) than groups II or IV. Hepatic IPC protects against distant renal IR injury through the blood stream-delivery of hepatic IPC-induced ROS, by inducing cytoprotective proteins, and by inhibiting inflammatory reactions.


Subject(s)
Animals , Intercellular Adhesion Molecule-1/genetics , Ischemic Preconditioning , Kidney/drug effects , Liver/blood supply , Male , Mice , Mice, Inbred C57BL , Nitric Oxide Synthase Type II/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Reperfusion Injury/metabolism , Tiopronin/pharmacology , Tumor Necrosis Factor-alpha/genetics
9.
Article in English | WPRIM | ID: wpr-123276

ABSTRACT

The purpose of this study is to determine 1) whether morphine postconditiong (MPostC) can attenuate the intercellular adhesion molecules-1 (ICAM-1) expression after reoxygenation injury and 2) the subtype(s) of the opioid receptors (ORs) that are involved with MPostC. Human umbilical vein endothelial cells (HUVECs) were subjected to 6 hr anoxia followed by 12 hr reoxygenation. Three morphine concentrations (0.3, 3, 30 microM) were used to evaluate the protective effect of MPostC. We also investigated blockading the OR subtypes' effects on MPostC by using three antagonists (a micro-OR antagonist naloxone, a kappa-OR antagonist nor-binaltorphimine, and a delta-OR antagonist naltrindole) and the inhibitor of protein kinase C (PKC) chelerythrine. As results, the ICAM-1 expression was significantly reduced in the MPostC (3, 30 microM) groups compared to the control group at 1, 6, 9, and 12 hours reoxygenation time. As a consequence, neutrophil adhesion was also decreased after MPostC. These effects were abolished by coadministering chelerythrine, nor-binaltorphimine or naltrindole, but not with naloxone. In conclusion, it is assumed that MPostC could attenuate the expression of ICAM-1 on endothelial cells during reoxygenation via the kappa and delta-OR (opioid receptor)-specific pathway, and this also involves a PKC-dependent pathway.


Subject(s)
Animals , Benzophenanthridines/pharmacology , Endothelial Cells/cytology , Endothelium, Vascular/cytology , Humans , Intercellular Adhesion Molecule-1/genetics , Morphine/pharmacology , Naloxone/pharmacology , Naltrexone/analogs & derivatives , Narcotic Antagonists/pharmacology , Narcotics/pharmacology , Protein Isoforms/metabolism , Protein Kinase C/antagonists & inhibitors , Receptors, Opioid/metabolism , Reperfusion Injury/metabolism , Signal Transduction/physiology , Umbilical Veins/cytology
10.
Braz. dent. j ; 21(6): 491-498, 2010. ilus, tab
Article in English | LILACS | ID: lil-572294

ABSTRACT

The aim of this study was to investigate the effects of low-level laser therapy (LLLT) by using gallium aluminum arsenide (GaAlAs) diode laser on human osteoblastic cells grown on titanium (Ti). Osteoblastic cells were obtained by enzymatic digestion of human alveolar bone and cultured on Ti discs for up to 17 days. Cells were exposed to LLLT at 3 J/cm2 (wavelength of 780 nm) at days 3 and 7 and non-irradiated cultures were used as control. LLLT treatment did not influence culture growth, ALP activity, and mineralized matrix formation. Analysis of cultures by epifluorescence microscopy revealed an area without cells in LLLT treated cultures, which was repopulated latter with proliferative and less differentiated cells. Gene expression of ALP, OC, BSP, and BMP-7 was higher in LLLT treated cultures, while Runx2, OPN, and OPG were lower. These results indicate that LLLT modulates cell responses in a complex way stimulating osteoblastic differentiation, which suggests possible benefits on implant osseointegration despite a transient deleterious effect immediately after laser irradiation.


Este estudo teve como objetivo investigar o efeito do laser diodo de gálio-alumínio-arsênio (GaAlAs) em células osteoblásticas humanas cultivadas sobre discos de Ti. Para tanto, células osteoblásticas foram obtidas por digestão enzimática de osso alveolar humano e cultivadas sobre discos de Ti por 17 dias. As células foram submetidas à irradiação no 3º e 7º dias na dose de 3 J/cm2 e comprimento de onda de 780 nm e células não irradiadas foram usadas como controle. A irradiação não alterou a proliferação celular, atividade de ALP e formação de matriz mineralizada. Microscopia por epifluorescência indicou que após 24 h da aplicação do laser, as culturas irradiadas apresentaram áreas sem células, que mais tarde foram repovoadas por células em fase de proliferação e menos diferenciadas. O laser aumentou a expressão gênica relativa da ALP, OC, BSP e BMP-7 e reduziu a de RUNX2, OPN e OPG. Os resultados indicam que a terapia com laser modula de forma complexa as respostas celulares, estimulando a diferenciação osteoblástica. Assim, é possível sugerir possíveis benefícios do laser na osseointegração de implantes de Ti apesar do efeito deletério às células imediatamente após a irradiação.


Subject(s)
Humans , Bone Matrix/growth & development , Gene Expression/radiation effects , Low-Level Light Therapy , Osseointegration/radiation effects , Osteoblasts/radiation effects , Analysis of Variance , Alkaline Phosphatase/biosynthesis , Alkaline Phosphatase/genetics , /biosynthesis , /genetics , Cells, Cultured/radiation effects , Collagen Type I/biosynthesis , Collagen Type I/genetics , Core Binding Factor Alpha 1 Subunit/biosynthesis , Core Binding Factor Alpha 1 Subunit/genetics , Integrin-Binding Sialoprotein/biosynthesis , Integrin-Binding Sialoprotein/genetics , Intercellular Adhesion Molecule-1/biosynthesis , Intercellular Adhesion Molecule-1/genetics , Lasers, Semiconductor/therapeutic use , Osteoblasts/metabolism , Osteocalcin/biosynthesis , Osteocalcin/genetics , Osteopontin/biosynthesis , Osteopontin/genetics , Osteoprotegerin/biosynthesis , Osteoprotegerin/genetics , RANK Ligand/biosynthesis , RANK Ligand/genetics , Statistics, Nonparametric , Titanium
11.
Article in English | WPRIM | ID: wpr-219392

ABSTRACT

Abstract In many clinical situations which cause thymic involution and thereby result in immune deficiency, T cells are the most often affected, leading to a prolonged deficiency of T cells. Since only the thymic-dependent T cell production pathway secures stable regeneration of fully mature T cells, seeking strategies to enhance thymic regeneration should be a key step in developing therapeutic methods for the treatment of these significant clinical problems. This study clearly shows that receptor activator of NF-kappaB ligand (RANKL) stimulates mouse thymic epithelial cell activities including cell proliferation, thymocyte adhesion to thymic epithelial cells, and the expression of cell death regulatory genes favoring cell survival, cell adhesion molecules such as ICAM-1 and VCAM-1, and thymopoietic factors including IL-7. Importantly, RANKL exhibited a significant capability to facilitate thymic regeneration in mice. In addition, this study demonstrates that RANKL acts directly on the thymus to activate thymus regeneration regardless of its potential influences on thymic regeneration through an indirect or systemic effect. In light of this, the present study provides a greater insight into the development of novel therapeutic strategies for effective thymus repopulation using RANKL in the design of therapies for many clinical conditions in which immune reconstitution is required.


Subject(s)
Animals , Cell Adhesion/drug effects , Cell Line , Cell Proliferation/drug effects , Cyclophosphamide/pharmacology , Down-Regulation/drug effects , Epithelial Cells/cytology , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Intercellular Adhesion Molecule-1/genetics , Interleukin-7/genetics , Male , Mice , Mice, Inbred C57BL , RANK Ligand/pharmacology , RNA, Messenger/genetics , Receptor Activator of Nuclear Factor-kappa B/genetics , Regeneration/drug effects , Thymus Gland/cytology , Up-Regulation/drug effects , Vascular Cell Adhesion Molecule-1/genetics , bcl-2-Associated X Protein/genetics , bcl-X Protein/genetics
12.
J Genet ; 2007 Dec; 86(3): 225-39
Article in English | IMSEAR | ID: sea-114248

ABSTRACT

We have studied DNA sequence variation in and around the genes ICAM1 and TNF, which play functional and correlated roles in inflammatory processes and immune cell responses, in 12 diverse ethnic groups of India, with a view to investigating the relative roles of demographic history and natural selection in shaping the observed patterns of variation. The total numbers of single nucleotide polymorphisms (SNPs) detected at the ICAM1 and TNF loci were 29 and 12, respectively. Haplotype and allele frequencies differed significantly across populations. The site frequency spectra at these loci were significantly different from those expected under neutrality, and showed an excess of intermediate-frequency variants consistent with balancing selection. However, as expected under balancing selection, there was no significant reduction of F(ST) values compared to neutral autosomal loci. Mismatch distributions were consistent with population expansion for both loci. On the other hand, the phylogenetic network among haplotypes for the TNF locus was similar to expectations under population expansion, while that for the ICAM1 was as expected under balancing selection. Nucleotide diversity at the ICAM1 locus was an order of magnitude lower in the promoter region, compared to the introns or exons, but no such difference was noted for the TNF gene. Thus, we conclude that the pattern of nucleotide variation in these genes has been modulated by both demographic history and selection. This is not surprising in view of the known allelic associations of several polymorphisms in these genes with various diseases, both infectious and noninfectious.


Subject(s)
Base Sequence , DNA Primers/genetics , Ethnic Groups/genetics , Female , Gene Frequency , Genetic Variation , Haplotypes , Humans , India , Intercellular Adhesion Molecule-1/genetics , Male , Phylogeny , Selection, Genetic , Tumor Necrosis Factor-alpha/genetics
13.
Acta bioquím. clín. latinoam ; 41(2): 193-202, abr.-jun. 2007. ilus, graf, tab
Article in Spanish | LILACS | ID: lil-633003

ABSTRACT

Se investigó la relación entre los polimorfismos de E-selectina, la molécula de adhesión vascular-1 (VCAM1) y la molécula de adhesión intercelular-1 (ICAM1) con el perfil de lípidos y marcadores clínicos de inflamación en artritis reumatoide (AR). Se incluyeron 60 pacientes con AR clasificados de acuerdo a los criterios del American College of Rheumatology (ACR, 1987) y 60 controles clínicamente sanos (CCS), no relacionados entre sí, definidos como población de mestizos mexicanos. Los genotipos se caracterizaron por la técnica de PCR-RFLP. La velocidad de sedimentación globular (VSG), factor reumatoideo (FR), concentración de fibrinógeno (FB), proteína C reactiva (PCR) y perfil de lípidos, se realizaron por métodos convencionales. El análisis estadístico se efectuó con SPSS v10.0. La VSG correlacionó con PCR, FR, FB y cHDL, (r=0,507; 0,296; 0,475 y -0,308, respectivamente); PCR con FB (r=0,613), p<0,05. El alelo 1238G se asoció con FR y Apo-B; y el alelo 721A, con cHDL y cLDL (p<0,05). Los datos muestran que los niveles de FB, cHDL, y los alelos 721A de ICAM1 y 1238G de VCAM1 se asocian con los marcadores clínicos de inflamación. Existen diferencias entre la distribución de los polimorfismos en este estudio y las reportadas para población oriental, caucásica y turca.


The genotypes were characterized using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) technique. The ESR (erythrocyte sedimentation rate), RF (rheumatoid factor), fibrinogen (FB), C-reactive protein (CRP) and lipid profile were measured by routine methods. Statistical analysis was performed using SPSS v10.0. The significant Pearson´s correlations were: ESR with CRP, RF, FB and HDLc, (r=0.507, 0.296, 0.475, and -0.308, respectively); CRP with FB (r=0.613), p<0.05. The results showed an association with A allele of ICAM1 polymorphism and serum levels of HDLc and LDLc; and Apo-B and FR showed an association with C allele of VCAM1 polymorphism (p<0.05). Data shows that FB and HDLc levels, and ICAM1 polymorphism allele 721A and VCAM1 polymorphism allele 1238G are associated with clinical inflammation markers in RA. Our Mexican-mestizo population showed differences with many reports (from English, American, Turkish, Japanese, Chinese, Italian, and Korean populations).


Subject(s)
Humans , Polymorphism, Genetic/genetics , Arthritis, Rheumatoid/genetics , Intercellular Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/genetics , E-Selectin/genetics , E-Selectin/blood , Reference Values , Rheumatoid Factor/blood , Fibrinogen , Intercellular Adhesion Molecule-1/blood , Vascular Cell Adhesion Molecule-1/blood , E-Selectin/physiology , Mexico
14.
Article in English | WPRIM | ID: wpr-37558

ABSTRACT

One of characteristic features of AIDS-related encephalitis and dementia is the infiltration of monocytes into the CNS. HIV-1 Tat was demonstrated to facilitate monocyte entry into the CNS. In this study, we examined the effect of HIV-1 Tat on the expression of adhesion molecules, generation of reactive oxygen species (ROS) and NF-kappaB activation in CRT-MG human astroglioma cells. Treatment of CRT-MG cells with HIV-1 Tat protein significantly increased protein and mRNA levels of ICAM-1 and VCAM-1, as measured by Western blot analysis and RT-PCR, indicating that Tat increases these protein levels at an mRNA level. In addition, Tat induced the activation of NF-kappaB in astrocytes. Treatment of CRT-MG with NF-kappaB inhibitors led to decrease in Tat-induced protein and mRNA expression of ICAM-1 and VCAM-1. Furthermore, HIV-1 Tat protein increased ROS generation. Inhibition of Tat-induced ROS generation by N-acetyl cysteine, vitamin C and diphenyl iodonium suppressed Tat-induced NF-kappaB activation, ICAM-1 and VCAM-1 expression, and monocyte adhesion in CRT-MG. These data indicate that HIV-1 Tat can modulate monocyte adhesiveness by increasing expression of adhesion molecules such as ICAM-1 and VCAM-1 via ROS- and NF-kappaB-dependent mechanisms in astrocytes.


Subject(s)
Vascular Cell Adhesion Molecule-1/genetics , Up-Regulation/drug effects , Transcription, Genetic/genetics , Reactive Oxygen Species/metabolism , NF-kappa B/metabolism , Monocytes/cytology , Intercellular Adhesion Molecule-1/genetics , Humans , HIV-1 , Gene Products, tat/pharmacology , Cell Line , Cell Adhesion/drug effects , Astrocytes/cytology
15.
Neurosciences. 2006; 11 (3): 187-190
in English | IMEMR | ID: emr-79740

ABSTRACT

To investigate the association of the 2 intracellular adhesion molecules-1 [ICAM-1] gene polymorphisms [thymidine/cytidine [T/C] 469 and guanosine/adenosine [G/A] 241] in Beh‡et's disease in Lebanon. We initiated the study in July 2003, and carried out the work in the research laboratory of Beirut Arab University, Beirut, Lebanon. We extracted the DNA by glass fiber matrix mini column. We amplified the ICAM gene by polymerase chain reaction [PCR] and tested the PCR products for the presence of the polymorphisms using a restriction enzyme specific for each polymorphism. We analyzed the results by agarose electrophoresis. We demonstrated the association of only one single nucleotide polymorphism [SNP] [K469] with Beh‡et's disease, while we could not detect the other SNP [G241A] in either controls or patients in the Lebanese population. The ICAM-1 gene polymorphism 469 T/C, but not 241 G/A, may encode risk for Beh‡et's disease in the Lebanese population


Subject(s)
Humans , Intercellular Adhesion Molecule-1/genetics , Polymorphism, Genetic , Thymidine , Cytidine , Guanosine , Adenosine
16.
Article in English | WPRIM | ID: wpr-29046

ABSTRACT

Intercellular adhesion molecule-1 (ICAM-1) is expressed on vascular endothelial cells and its expression increases during the inflammatory response in patients with active Behcet's disease (BD). The ICAM1 gene mutations are associated with BD in Caucasians, but clinical features of the mutation phenotype are unknown. We analyzed ICAM1 polymorphisms in Korean BD patients to determine if there was an association between particular mutations and clinical symptoms. The prevalence of ICAM1R241G and ICAM1K469E polymorphisms was determined among 197 patients with BD and 248 healthy controls using BsrG1 and BstU1 PCR-RFLP. The frequency of both genotypes ICAM1469 * K/ * E and ICAM-1469 * E/ * E was significantly higher in BD patients compared with controls (66.0% vs 52.4%, p=0.004, OR=1.28, 95% CI 1.08-1.50) and the allele frequency of ICAM1469 * E was higher in patients with skin lesions (0.41), genital ulcers (0.41), vasculitis (0.43), ocular lesions (0.41) and arthritis (0.39) than in controls (0.31). Only one heterozygote, ICAM1241G/R, was detected in BD patients but the ICAM1241 * R mutation was not found in any of the 248 healthy controls. These results show that the ICAM1 mutation is associated with BD susceptibility, and is another genetic risk factor for BD among the Korean population.


Subject(s)
Adult , Behcet Syndrome/ethnology , Female , Gene Frequency , Genetic Predisposition to Disease/epidemiology , Humans , Intercellular Adhesion Molecule-1/genetics , Korea/epidemiology , Male , Middle Aged , Phenotype , Polymorphism, Restriction Fragment Length , Risk Factors
17.
Article in English | WPRIM | ID: wpr-172827

ABSTRACT

Prior ischemia leads to resistance against subsequent ischemic insults. The mechanisms that underlie this adaptive response remain unidentified. Thus, we studied whether the reduced susceptibility of mice previously subjected to the ischemia to ischemia/ reperfusion injury is related with altered inflammatory responses. Thirty minutes of bilateral kidney ischemia results in significantly increased plasma creatinine and blood urea nitrogen levels in BALB/c male mice. There is severe disruption of actin cytoskeleton of proximal tubular cells in the outer stripe of the outer medulla 24 hours post-ischemia. When mice are subjected to 30 minutes of bilateral ischemia 8 days later, there is no increase in plasma creatinine and blood urea nitrogen levels and the post-ischemic disruption of actin cytoskeleton of proximal tubular cells is much less. Inflammatory responses have highly implicated with ischemia/reperfusion injury. Ischemia results in the increased tissue myeloperoxidase (MPO) activity that is a marker of leukocyte infiltration. There is, however, no the post-ischemic increase of MPO activity in kidneys previously subjected to ischemia. Post-ischemic expression of tissue intercellular adhesion molecule-1 (ICAM-1) is greater in the kidney previously sham-operated than in the kidneys previously subjected to ischemia. In conclusion, prior ischemia protects kidney function and morphology against subsequent ischemia 8 days later. The resistance is associated with the reduced post-ischemic leukocyte infiltration due to the reduced post-ischemic ICAM-1 expression.


Subject(s)
Adaptation, Physiological , Animals , Blood Urea Nitrogen , Creatinine/blood , Gene Expression Regulation , Inflammation/physiopathology , Intercellular Adhesion Molecule-1/genetics , Ischemia/physiopathology , Kidney/blood supply , Kidney Tubules, Proximal/physiopathology , Male , Mice , Mice, Inbred BALB C , Peroxidase/metabolism , Renal Circulation , Reperfusion Injury
18.
Article in English | WPRIM | ID: wpr-13043

ABSTRACT

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, known as statins, are widely used for primary and secondary prevention of coronary artery atherosclerosis. Pathogenesis of atherosclerosis is multistep processes where transendothelial migration of various leukocytes including monocytes is a crucial step. Interferon-gamma(IFN-gamma) contributes in this process by activating macrophages and T-lymphocytes, and by inducing adhesion molecules in vascular endothelial and smooth muscle cells. In this study we investigated the expression of intercellular cell adhesion molecule- 1 (ICAM-1) in transformed endothelial cell line ECV304 cells as influenced by lovastatin, tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma. Results show that lovastatin suppresses expression of ICAM-1 by inhibiting the IFN-gamma-induced extracellular signal-regulated kinase (ERK) p44/p42-STAT1 signaling pathway. In cells treated with lovastatin and IFN-gamma.ICAM-1 was expressed at a lower level than in cells treated with IFN-gamma alone. However, lovastatin does not reduce TNF-alpha induced expression of ICAM-1. A similar result was observed in cells treated with the MEKK inhibitor PD98059 and IFN-gamma. Cis-acting DNA sequence elements were identified in the 5'-flanking region of the ICAM-1 promoter that mediate inhibition by lovastatin; these sequences map to the IFN-gamma activated site which also binds the STAT1 homodimer. However, lovastatin did not inhibit IFN-gamma-mediated induction of the Y701 phosphorylated form of STAT1. But lovastatin does inhibit the IFN-gamma-mediated phosphorylation of ERK1/ERK2 (T202/Y204) and S727 phosphorylation of STAT1. TNF-alpha does not induce phosphorylation of ERK1/ERK2 and S727 in ECV304 and smooth muscle cells. The results provide the evidences that statins may have beneficial effects by inhibiting IFN-gamma action in atherosclerotic process


Subject(s)
Animals , Cell Line , DNA-Binding Proteins/metabolism , Endothelium, Vascular/cytology , Gene Expression Regulation/drug effects , Intercellular Adhesion Molecule-1/genetics , Interferon-gamma/antagonists & inhibitors , Lovastatin/pharmacology , Mitogen-Activated Protein Kinases/metabolism , Myocytes, Smooth Muscle/cytology , Phosphorylation/drug effects , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , Rats , Recombinant Proteins , Trans-Activators/metabolism , Tumor Necrosis Factor-alpha/pharmacology
19.
Article in English | WPRIM | ID: wpr-153277

ABSTRACT

OBJECTIVES: In HFRS, there is a varying degree of disseminated intravascular coagulation which was evident in the early phase of the illness. It is believed also that DIC would be the consequence, at least in part, of functional changes of endothelium resulting in kinin activation and clinical syndrome. This study investigated the role of adhesion molecule in the pathogenesis of Hantaan virus-related disease. METHODS: The expression of ICAM-1 antigen on the cell membrane of human umbilical vein endothelial cells was assessed by immunohistochemistry, and ICAM-1 mRNA in the endothelial cells was assessed by in situ hybridization after Hantaan virus infection (2.6 x 10(4) PFU/mL) with the time course. RESULTS: In immunohistochemistry, the number of ICAM-1 positive cells increased with time during the 12 or 24 hours after infection. 5 to 10% of HUVECs had been positive after 12-24 hours and the number of positive cells decreased abruptly after 24 hours. Hantaan antigen had been noticed after 12 hours focally on the HUVECs but continued to proliferate into day 7 post-infection when most of HUVECs were infected by Hantaan virus. In situ hybridization showed identical patterns of ICAM-1 mRNA expression after Hantaan virus infection. CONCLUSION: It implies that the Hantaan virus infection on HUVECs would express more ICAM-1 on their surface and implicated in the pathogenesis of early clinical syndrome of HFRS.


Subject(s)
Cell Line , Endothelium, Vascular/virology , Endothelium, Vascular/immunology , Gene Expression , Hantaan virus/pathogenicity , Hemorrhagic Fever with Renal Syndrome/immunology , Hemorrhagic Fever with Renal Syndrome/genetics , Hemorrhagic Fever with Renal Syndrome/etiology , Humans , Immunohistochemistry , In Situ Hybridization , Intercellular Adhesion Molecule-1/metabolism , Intercellular Adhesion Molecule-1/genetics , RNA, Messenger/metabolism , RNA, Messenger/genetics
SELECTION OF CITATIONS
SEARCH DETAIL