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BACKGROUND@#To achieve optimal bone marrow engraftment during bone marrow transplantation, migration of donor bone marrow cells (BMCs) toward the recipient’s bone marrow is critical. Despite the enhanced engraftment of BMCs by co-administration of mesenchymal stem cells (MSCs), the efficiency can be variable depending on MSC donor. The purpose of this study is to examine the functional heterogeneity of tonsil-derived MSCs (TMSCs) and to identify a marker to evaluate efficacy for the enhancement of BMC migration. @*METHODS@#To examine the donor-to-donor variation of TMSCs in potentiating BMC migration, we isolated TMSCs from 25 independent donors. Transcriptome of TMSCs and proteome of conditioned medium derived from TMSC were analyzed. @*RESULTS@#Enhanced BMC migration by conditioned medium derived from TMSCs was variable depending on TMSC donor. The TMSCs derived from 25 donors showed distinct expression profiles compared with other cells, including fibroblasts, adipose-derived MSCs and bone marrow–derived MSCs. TMSCs were distributed in two categories: high- and low-efficacy groups for potentiating BMC migration. Transcriptome analysis of TMSCs and proteome profiles of conditioned medium derived from TMSCs revealed higher expression and secretion of matrix metalloproteinase (MMP) 1 in the high-efficacy group. MMP1 knockdown in TMSCs abrogated the supportive efficacy of conditioned medium derived from TMSC cultures in BMC migration. @*CONCLUSION@#These data suggest that secreted MMP1 can be used as a marker to evaluate the efficacy of TMSCs in enhancing BMC migration. Furthermore, the strategy of analyzing transcriptomes and proteomes of the MSCs may be useful to set the standard for donor variation.
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BACKGROUND@#Mast cells are immune sentinels in the skin that respond to a wide range of pathological and environmental stimuli; they owe their function to the expression of Toll-like receptors (TLRs). We previously found that tonsilderived mesenchymal stem cells (T-MSCs) were able to effectively attenuate TLR7-mediated skin inflammation in mice, which was accompanied by an increase in mast cell number. The present study investigated whether T-MSC extracellular vesicles, such as exosomes, are able to regulate mast cell activation in response to TLR7 stimulation. @*METHODS@#The HMC-1 human mast cell line was treated with a TLR7 agonist in the presence or absence of T-MSC exosomes, and the levels of expressed inflammatory cytokines were assessed. Additionally, mice were repeatedly injected with a TLR7 agonist with or without interval treatments with T-MSC exosomes and assessed dermal distribution of mast cells and related immune cells. @*RESULTS@#We showed that T-MSC exosomes containing microRNAs that target inflammatory cytokines significantly reduced the expression of inflammatory cytokines in TLR7 agonist-treated HMC-1 cells. In addition, T-MSC exosomes inhibited the increase in the number of both dermal mast cells and CD14-positive cells in TLR7 agonist-treated mice. @*CONCLUSION@#Our data suggest that T-MSC exosomes have regulatory effects on mast cell activation under inflammatory conditions, including TLR7 stimulation.
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BACKGROUND@#Therapeutic strategies that can promote platelet production are in demand to enhance clinical outcomes of bone marrow transplantation (BMT). Our research group has studied human tonsil-derived mesenchymal stem cells (TMSCs) and their effectiveness in promoting bone marrow (BM) engraftment. Here, we analyzed the effects of T-MSCs on platelet production and hemostasis. @*METHODS@#Donor BM cells (BMCs) were isolated from C57BL/6 mice and transplanted with or without T-MSCs to BALB/c recipient mice. Mice were sacrificed and blood cells were counted using an Auto Hematology Analyzer. Femur sections were stained with CD41 antibody to analyze megakaryocytes in the BM. Growth factor secretion from MSCs was analyzed using the Quantibody Array. Effects of T-MSC conditioned medium (CM) on megakaryopoiesis were investigated using the MegaCult assay. In a mouse model of BMT, T-MSC CM was injected with or without anti-placental growth factor (a-PlGF) blocking antibody, and blood cell numbers and coagulation were analyzed. @*RESULTS@#T-MSC co-transplantation increased percent survival of BMT mice. Platelet numbers were significantly lower in the BMC-only group, whereas T-MSC co-transplantation restored circulating platelets to levels similar to those of the control group. Significantly reduced numbers of CD41 ? megakaryocytes in Bu-Cy and BMC groups were increased by T-MSC co-transplantation. PlGF secretion from T-MSCs were detected and enhanced megakaryopoiesis, platelet production, and coagulation by T-MCS CM were disrupted in the presence of the a-PlGF blocking antibody. @*CONCLUSION@#We demonstrated the effectiveness of T-MSC co-transplantation in promoting platelet production and coagulation after BMT. These findings highlight the potential therapeutic relevance of T-MSCs for preventing thrombocytopenia after BMT.
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BACKGROUND@#The advantages of tonsil-derived mesenchymal stem cells (TMSCs) over other mesenchymal stem cells (MSCs) include higher proliferation rates, various differentiation potentials, efficient immune-modulating capacity, and ease of obtainment. Specifically, TMSCs have been shown to differentiate into the endodermal lineage. Estrogen deficiency is a major cause of postmenopausal osteoporosis and is associated with higher incidences of ischemic heart disease and cerebrovascular attacks during the postmenopausal period. Therefore, stem cell-derived, estrogen-secreting cells might be used for estrogen deficiency. @*METHODS@#Here, we developed a novel method that utilizes retinoic acid, insulin-like growth factor-1, basic fibroblast growth factor, and dexamethasone to evaluate the differentiating potential of TMSCs into estrogen-secreting cells. The efficacy of the novel differentiating method for generation of estrogen-secreting cells was also evaluated with bone marrow- and adipose tissue-derived MSCs. @*RESULTS@#Incubating TMSCs in differentiating media induced the gene expression of cytochrome P450 19A1 (CYP19A1), which plays a key role in estrogen biosynthesis, and increased 17b-estradiol secretion upon testosterone addition. Furthermore, CYP11A1, CYP17A1, and 3b-hydroxysteroid dehydrogenase type-1 gene expression levels were significantly increased in TMSCs. In bone marrow-derived and adipose tissue-derived MSCs, this differentiation method also induced the gene expression of CYP19A1, but not CYP17A1, suggesting TMSCs are a superior source for estrogen secretion. @*CONCLUSION@#These results imply that TMSCs can differentiate into functional estrogen-secreting cells, thus providing a novel, alternative cell therapy for estrogen deficiency.
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Background@#Mast cells are skin immune sentinels located in the upper dermis, where wheal formation and sensory nerve stimulation take place. Skin inflammation is occasionally accompanied by mast cell-driven responses with wheals, angioedema, or both. Immunoglobulin E (IgE) antibodies are regarded as typical stimuli to drive mast cell activation. However, various causative factors, including microbial infections, can drive IgE-independent mast cell response. When infected, the innate immunity orchestrates an immune response by activating receptor signaling via Toll-like receptors (TLRs). @*Objective@#In this study, we determined the effect of TLR7 stimulation on mast cells to investigate the possible mechanism of IgE-independent inflammatory response. @*Methods@#Human mast cell (HMC) line, HMC-1 cells were treated with TLR7 agonist and the morphologic alteration was observed in transmission electron microscopy. Further, TLR7 agonist treated HMC-1 cells were conducted to RNA sequencing to compare transcriptomic features. @*Results@#HMC-1 cells treated with TLR7 agonist reveals increase of intracellular vesicles, lipid droplets, and ribosomes. Also, genes involved in pro-inflammatory responses such as angiogenesis are highly expressed, and Il12rb2 was the most highly upregulated gene. @*Conclusion@#Our data suggest that TLR7 signaling on mast cells might be a potential therapeutic target for mast cell-driven, IgE-independent skin inflammation.
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Background@#Hot springs have been traditionally used as an alternative treatment for a wide range of diseases, including rheumatoid arthritis, bronchial asthma, diabetes, hypertension, psoriasis and atopic dermatitis. However, the clinical effects and therapeutic mechanisms associated with hot springs remain poorly defined. @*Objective@#The purpose of this study was to demonstrate the different effects of hot springs on cellular viability and secretion of inflammatory cytokines on keratinocyte in two geographically representative types of hot springs: NaHCO3 -type and NaCl-type, which are the most common types in South Korea. @*Methods@#We performed WST-1, BrdU measurements, human inflammatory cytokine arrays and enzyme-linked immunosorbent assay in HaCaT cells stimulated with toll-like receptor 3 by polyinosinic-polycytidylic acid. @*Results@#The interaction effects of cell viability and cell proliferation were not significantly different regardless of polyinosinic-polycytidylic acid stimulation and cultured hot springs type. Cytokine array and enzyme-linked immunosorbent assay analysis showed increased expression of inflammatory cytokines such as interleukin-6 and granulocyte-macrophage colony-stimulating factor by polyinosinic-polycytidylic acid stimulation, with expression levels differing according to hot springs hydrochemical composition. Cytokine reduction was not significant. @*Conclusion@#The effects and mechanisms of hot springs treatment in keratinocytes were partially elucidated.
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BACKGROUND@#The advantages of tonsil-derived mesenchymal stem cells (TMSCs) over other mesenchymal stem cells (MSCs) include higher proliferation rates, various differentiation potentials, efficient immune-modulating capacity, and ease of obtainment. Specifically, TMSCs have been shown to differentiate into the endodermal lineage. Estrogen deficiency is a major cause of postmenopausal osteoporosis and is associated with higher incidences of ischemic heart disease and cerebrovascular attacks during the postmenopausal period. Therefore, stem cell-derived, estrogen-secreting cells might be used for estrogen deficiency. @*METHODS@#Here, we developed a novel method that utilizes retinoic acid, insulin-like growth factor-1, basic fibroblast growth factor, and dexamethasone to evaluate the differentiating potential of TMSCs into estrogen-secreting cells. The efficacy of the novel differentiating method for generation of estrogen-secreting cells was also evaluated with bone marrow- and adipose tissue-derived MSCs. @*RESULTS@#Incubating TMSCs in differentiating media induced the gene expression of cytochrome P450 19A1 (CYP19A1), which plays a key role in estrogen biosynthesis, and increased 17b-estradiol secretion upon testosterone addition. Furthermore, CYP11A1, CYP17A1, and 3b-hydroxysteroid dehydrogenase type-1 gene expression levels were significantly increased in TMSCs. In bone marrow-derived and adipose tissue-derived MSCs, this differentiation method also induced the gene expression of CYP19A1, but not CYP17A1, suggesting TMSCs are a superior source for estrogen secretion. @*CONCLUSION@#These results imply that TMSCs can differentiate into functional estrogen-secreting cells, thus providing a novel, alternative cell therapy for estrogen deficiency.
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Background@#Mast cells are skin immune sentinels located in the upper dermis, where wheal formation and sensory nerve stimulation take place. Skin inflammation is occasionally accompanied by mast cell-driven responses with wheals, angioedema, or both. Immunoglobulin E (IgE) antibodies are regarded as typical stimuli to drive mast cell activation. However, various causative factors, including microbial infections, can drive IgE-independent mast cell response. When infected, the innate immunity orchestrates an immune response by activating receptor signaling via Toll-like receptors (TLRs). @*Objective@#In this study, we determined the effect of TLR7 stimulation on mast cells to investigate the possible mechanism of IgE-independent inflammatory response. @*Methods@#Human mast cell (HMC) line, HMC-1 cells were treated with TLR7 agonist and the morphologic alteration was observed in transmission electron microscopy. Further, TLR7 agonist treated HMC-1 cells were conducted to RNA sequencing to compare transcriptomic features. @*Results@#HMC-1 cells treated with TLR7 agonist reveals increase of intracellular vesicles, lipid droplets, and ribosomes. Also, genes involved in pro-inflammatory responses such as angiogenesis are highly expressed, and Il12rb2 was the most highly upregulated gene. @*Conclusion@#Our data suggest that TLR7 signaling on mast cells might be a potential therapeutic target for mast cell-driven, IgE-independent skin inflammation.
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Background@#Hot springs have been traditionally used as an alternative treatment for a wide range of diseases, including rheumatoid arthritis, bronchial asthma, diabetes, hypertension, psoriasis and atopic dermatitis. However, the clinical effects and therapeutic mechanisms associated with hot springs remain poorly defined. @*Objective@#The purpose of this study was to demonstrate the different effects of hot springs on cellular viability and secretion of inflammatory cytokines on keratinocyte in two geographically representative types of hot springs: NaHCO3 -type and NaCl-type, which are the most common types in South Korea. @*Methods@#We performed WST-1, BrdU measurements, human inflammatory cytokine arrays and enzyme-linked immunosorbent assay in HaCaT cells stimulated with toll-like receptor 3 by polyinosinic-polycytidylic acid. @*Results@#The interaction effects of cell viability and cell proliferation were not significantly different regardless of polyinosinic-polycytidylic acid stimulation and cultured hot springs type. Cytokine array and enzyme-linked immunosorbent assay analysis showed increased expression of inflammatory cytokines such as interleukin-6 and granulocyte-macrophage colony-stimulating factor by polyinosinic-polycytidylic acid stimulation, with expression levels differing according to hot springs hydrochemical composition. Cytokine reduction was not significant. @*Conclusion@#The effects and mechanisms of hot springs treatment in keratinocytes were partially elucidated.
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BACKGROUND: After the introduction of the meningococcal ACWY-CRM197 conjugate vaccine (MenACWY-CRM) in 2012 and the meningococcal ACWY-diphtheria toxoid conjugate vaccine (MenACWY-DT) in 2014, immunization was recommended for certain high-risk groups including new military recruits in Korea. However, comparative immunogenicity studies for these vaccines have not been performed in Korea. Here, we compared the immunogenicity of these two vaccines in healthy adults. METHODS: A total of 64 adults, 20–49 years of age, were randomly divided into two groups (1:1) to receive either of the two vaccines. The sera were obtained before and 1 month after vaccination and tested for serogroup-specific serum bactericidal activity using baby rabbit complement. RESULTS: There were no significant differences post-vaccination in the geometric mean indices and the seropositive rate to all serogroups between the vaccines. The proportion of seropositive subjects after vaccination ranged from 88% to 100%. CONCLUSION: Both meningococcal conjugate vaccines showed good immunogenicity in healthy Korean adults without statistically significant differences. Further investigations for serotype distribution of circulating meningococci and the immune interference between other diphtheria toxin-containing vaccines concomitantly used for military recruits are needed to optimize immunization policies. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0002460
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Adulto , Humanos , Proteínas do Sistema Complemento , Difteria , Imunização , Serviços de Informação , Coreia (Geográfico) , Vacinas Meningocócicas , Militares , Sorogrupo , Vacinação , Vacinas , Vacinas ConjugadasRESUMO
BACKGROUND: The liver is an organ with remarkable regenerative capacity; however, once chronic fibrosis occurs, liver failure follows, with high mortality and morbidity rates. Continuous exposure to proinflammatory stimuli exaggerates the pathological process of liver failure; therefore, immune modulation is a potential strategy to treat liver fibrosis. Mesenchymal stem cells (MSCs) with tissue regenerative and immunomodulatory potential may support the development of therapeutics for liver fibrosis. METHODS: Here, we induced hepatic injury in mice by injecting carbon tetrachloride (CCl₄) and investigated the therapeutic potential of conditionedmedium from tonsil-derivedMSCs (T-MSCCM). In parallel, we used recombinant human IL-1Ra,which, as we have previously shown, is secreted exclusively from T-MSCs and resolves the fibrogenic activation of myoblasts. Hepatic inflammation and fibrosis were determined by histological analyses using H&E and Picro-Sirius Red staining. RESULTS: The results demonstrated that T-MSC CM treatment significantly reduced inflammation as well as fibrosis in the CCl₄-injured mouse liver. IL-1Ra injection showed effects similar to T-MSC CM treatment, suggesting that T-MSC CM may exert anti-inflammatory and anti-fibrotic effects via the endogenous production of IL-1Ra. The expression of genes involved in fibrosis was evaluated, and the results showed significant induction of alpha-1 type I collagen, transforming growth factor beta, and tissue inhibitor of metalloproteases 1 upon CCl₄ injection, whereas treatment with T-MSC CM or IL-1Ra downregulated their expression. CONCLUSION: Taken together, these data support the therapeutic potential of T-MSC CM and/or IL-1Ra for the alleviation of liver fibrosis, as well as in treating diseases involving organ fibrosis.
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Animais , Humanos , Camundongos , Tetracloreto de Carbono , Colágeno Tipo I , Meios de Cultivo Condicionados , Fibrose , Inflamação , Proteína Antagonista do Receptor de Interleucina 1 , Cirrose Hepática , Falência Hepática , Fígado , Células-Tronco Mesenquimais , Metaloproteases , Mortalidade , Mioblastos , Fator de Crescimento Transformador betaRESUMO
Human gut microbial community is playing a critical role in human health and associated with different human disease. In parallel, probiotics, antibiotics, and antipyretic analgesics (AAs) were developed to improve human health or cure human diseases. We therefore examined how probiotics, antibiotics, and AAs influence to the gut microbiota. Three independent case/control studies were designed from the cross-sectional cohort data of 1,463 healthy Koreans. The composition of the gut microbiota in each case and control group was determined via 16S ribosomal RNA Illumina next-generation sequencing. The correlation between microbial taxa and the consumption of each drug was tested using zero-inflated Gaussian mixture models, with covariate adjustment of age, sex, and body mass index (BMI). Probiotics, antibiotics, and AAs consumption yielded the significant differences in the gut microbiota, represented the lower abundance of Megasphaera in probiotics, the higher abundance of Fusobacteria in antibiotics, and the higher abundance of Butyrivibrio and Verrucomicrobia in AAs, compared to each control group. The reduction of Erysipelotrichaceae family was common in three drugs consumption.
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Humanos , Analgésicos , Antibacterianos , Índice de Massa Corporal , Butyrivibrio , Estudos de Coortes , Fusobactérias , Microbioma Gastrointestinal , Megasphaera , Probióticos , RNA Ribossômico 16S , VerrucomicrobiaRESUMO
Obesity that caused by high-fat diet, heredity, drinking, or lack of exercise is related to metabolic syndrome, insulin resistance, type 2 diabetes and cardiovascular disease and it becomes a serious social problem. Although obesity shows low-grade chronic inflammation which induces from immune response in adipose tissue, relation between inflammation and pathogenesis of obesity has not been incompletely understood. Therefore, study for immune response in obesity is essential to design effective therapeutic strategy.
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Tecido Adiposo , Doenças Cardiovasculares , Dieta Hiperlipídica , Ingestão de Líquidos , Hereditariedade , Inflamação , Resistência à Insulina , Obesidade , Problemas SociaisRESUMO
BACKGROUND: Although the therapeutic mechanism of balneotherapy for atopic dermatitis has not been clarified, many atopic patients who visit thermomineral springs have shown clinical improvements. OBJECTIVE: This study was aimed to evaluate the immunomodulatory effect of thermomineral water balneotherapy on the atopic dermatitis murine model. METHODS: The oxazolone-induced atopic dermatitis murine model was used to evaluate the therapeutic effect of balneotherapy with Deokgu thermomineral water compared with distilled water. Histologic evaluation and confocal microscopic imaging were performed to analyze the lesional expression of cluster-of-differentiation (CD)4 and forkhead box p3 (Foxp3). Lesional mRNA expression of interleukin (IL) 33, thymic stromal lymphopoietin (TSLP), and Foxp3 was evaluated by real-time reverse transcription polymerase chain reaction. RESULTS: Compared with the distilled water bath group, confocal microscopic evaluation of CD4 and Foxp3 merged images showed increased expression of regulatory T cells in the thermomineral balneotherapy group. The lesional mRNA level of IL-33 showed a reduced trend in the thermomineral balneotherapy group, whereas the level of mRNA of Foxp3 was increased. TSLP showed a decreased trend in both distilled water and thermomineral water bath groups. There was a trend of reduced expression in lesional IL-33 mRNA but increased cell count of CD4+ Foxp3+ regulatory T cells in thermomineral balneotherapy compared with distilled water bath. CONCLUSION: Therefore, thermomineral balneotherapy can be an effective and safe adjuvant therapeutic option for atopic dermatitis.
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Humanos , Balneologia , Banhos , Contagem de Células , Dermatite , Dermatite Atópica , Imunomodulação , Interleucinas , Reação em Cadeia da Polimerase , Transcrição Reversa , RNA Mensageiro , Linfócitos T Reguladores , ÁguaRESUMO
Background: The beneficial clinical effects of Korean hot spring spa therapy, as well as their underlying mechanisms are still poorly understood. We performed a series of clinical and laboratory investigations for better understanding of the clinical effects as well as possible mechanisms of their beneficial effects. Methods: HaCaT cells were prepared and treated with TLR agonist in the presence or absence of HS water for quantification of IL-6, IL-8, GM-CSF, and TNF-α levels. The serum levels of IFN-ɤ, IL-4, IL-5, and IgE were measured. CD4+ naïve cells were allowed to polarize into Th1, Th2, Th17, and Treg cells, and CD4+ and CFSE+ cells were measured for the degree of proliferation. Total RNA from the lesional skin was transcribed into cDNA using a reverse transcription system, and RT-PCR was performed subsequently. Confocal microscopy and RT-PCR were utilized to evaluate the target skin localization of Th cell subsets and associated inflammatory cytokine milieu. Results: Treatment with agonists of TLR 1 through 6 induced attenuation of cytokine production in the exposure to HS water. HS water suppressed the proliferation of Th1, Th2, and Th17 cells with anti-CD3 stimulation, while proliferation and differentiation to Treg cells were promoted under HS water treatment. On RT-PCR of the lesional skin, thymic stromal lymphopoietin (TSLP) mRNA decreased dramatically after bathing with HS. IL-33 mRNA decreased markedly in HS water group as compared to control group. Foxp3 mRNA expression, same as in confocal microscopic finding, showed tendency to increase more in HS. Conclusions: HS water suppressed the proliferation of Th1, Th2, and Th17 cells. In contrast, proliferation and differentiation to Treg cells were promoted under HS water treatment. These results indicate that HS water may affect the distribution of the helper T cells in the immune response, by suppressing the polarization of the Th1, Th2, and Th17 cells. Also, APC induced TNF-α and IL-6 levels were reduced in the presence of HS water. These results showed that TLR-triggered inflammatory responses in APCs might also be modulated under HS water treatment. Overall, our findings suggest that HS spa therapy could be an effective and safe modality for the management of adult AD.
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<b>Background: </b>The beneficial clinical effects of Korean hot spring spa therapy, as well as their underlying mechanisms are still poorly understood. We performed a series of clinical and laboratory investigations for better understanding of the clinical effects as well as possible mechanisms of their beneficial effects.<BR><b>Methods:</b> HaCaT cells were prepared and treated with TLR agonist in the presence or absence of HS water for quantification of IL-6, IL-8, GM-CSF, and TNF-<i>α</i> levels. The serum levels of IFN-ɤ, IL-4, IL-5, and IgE were measured. CD4<sup>+</sup> naïve cells were allowed to polarize into Th1, Th2, Th17, and Treg cells, and CD4<sup>+</sup> and CFSE<sup>+</sup> cells were measured for the degree of proliferation. Total RNA from the lesional skin was transcribed into cDNA using a reverse transcription system, and RT-PCR was performed subsequently. Confocal microscopy and RT-PCR were utilized to evaluate the target skin localization of Th cell subsets and associated inflammatory cytokine milieu.<BR><b>Results: </b>Treatment with agonists of TLR 1 through 6 induced attenuation of cytokine production in the exposure to HS water. HS water suppressed the proliferation of Th1, Th2, and Th17 cells with anti-CD3 stimulation, while proliferation and differentiation to Treg cells were promoted under HS water treatment. On RT-PCR of the lesional skin, thymic stromal lymphopoietin (TSLP) mRNA decreased dramatically after bathing with HS. IL-33 mRNA decreased markedly in HS water group as compared to control group. Foxp3 mRNA expression, same as in confocal microscopic finding, showed tendency to increase more in HS.<BR><b>Conclusions:</b> HS water suppressed the proliferation of Th1, Th2, and Th17 cells. In contrast, proliferation and differentiation to Treg cells were promoted under HS water treatment. These results indicate that HS water may affect the distribution of the helper T cells in the immune response, by suppressing the polarization of the Th1, Th2, and Th17 cells. Also, APC induced TNF-<i>α</i> and IL-6 levels were reduced in the presence of HS water. These results showed that TLR-triggered inflammatory responses in APCs might also be modulated under HS water treatment. Overall, our findings suggest that HS spa therapy could be an effective and safe modality for the management of adult AD.
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Heat shock protein 90 (HSP90) is involved in conformational and structural maturation of signalling molecules and transcription factors in immune reaction. HSP90 inhibitors induce immune modulation via anti-inflammatory effect, regulating humoral and cellular immune responses. Therefore, HSP90 inhibitors potentially useful target for the autoimmune disease and chronic inflammatory diseases.
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Doenças Autoimunes , Proteínas de Choque Térmico , Imunidade Celular , Interleucina-17 , Fatores de TranscriçãoRESUMO
BACKGROUND: Balneotherapy, although not a well-established dermatological treatment, is thought to have therapeutic properties for psoriasis and is used as an alternative treatment modality throughout the world. OBJECTIVE: To evaluate the mechanism underlying the therapeutic immunologic effects of thermomineral water. METHODS: A murine model of imiquimod-induced psoriasis-like skin inflammation was used for evaluating the therapeutic effects of balneotherapy with Hae-Un-Dae hot spring mineral water. The clinical improvements were evaluated by a dermatologist. Lesional cytokines, including interleukin (IL)-17A, IL-23, and IL-22, were quantitatively measured by real-time reverse transcriptase polymerase chain reaction. Serum levels of interferon-gamma, IL-4, IL-5, and IL-17A were measured by enzyme-linked immunosorbent assay. T cell proportions in the spleen were evaluated by flow cytometry, and histopathological evaluation of the skin was also performed. RESULTS: The mineral water balneotherapy group showed faster improvement in skin erythema and scales than the distilled water bathing group. A substantial reduction was observed in the lesional mRNA levels of IL-17A and IL-23 in the mineral water group. Serum levels of IL-4 and IL-5 were significantly decreased in the mineral water group but not in the distilled water group. Normalized T cell proportions were observed after bathing. CONCLUSION: Balneotherapy showed immunomodulatory effects in a psoriasis-like murine model. Balneotherapy suppressed lesional IL-23 and IL-17A, which are important cytokines in the pathogenesis of psoriasis. These results suggest that balneotherapy can be used as an effective and safe treatment for psoriasis.
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Balneologia , Banhos , Citocinas , Ensaio de Imunoadsorção Enzimática , Eritema , Citometria de Fluxo , Fontes Termais , Imunomodulação , Inflamação , Interferon gama , Interleucina-17 , Interleucina-23 , Interleucina-4 , Interleucina-5 , Interleucinas , Águas Minerais , Psoríase , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Mensageiro , Pele , Baço , Água , Pesos e MedidasRESUMO
Angiostatin is derived from enzymatic degradation of plasminogen and it has endogenous anti-angiogenic properties. Although tumor cells, macrophages, platelets, and neutrophils generate high amount of angiostatin, its expression is increased in inflammatory conditions. Moreover, angiostatin binds to integrin alpha(v)beta(3), ATP synthase, and angiomotin, which expressed on neutrophils. Activated neutrophils are essential to innate immune response, but also cause tissue damage through production of reactive oxygen species (ROS) and increase lifespan. In this article, it suggests several mechanism of angiostatin as immune regulator for neutrophils in inflammatory conditions; complex with integrin alpha(v)beta(3) and F(1)F(0) ATP synthase on lipid raft, attenuate polarization, and ROS production. These data provide possible exploit of double-edged role of neutrophils in acute inflammatory pathologies to preserve beneficial effect and minimize tissue damage.
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Trifosfato de Adenosina , Angiostatinas , Apoptose , Imunidade Inata , Integrina alfaVbeta3 , Macrófagos , Ativação de Neutrófilo , Neutrófilos , Patologia , Plasminogênio , Espécies Reativas de OxigênioRESUMO
PURPOSE: Asthma is a chronic inflammatory disease of the airways associated with structural changes and airway remodeling. Interleukin (IL)-9 has pleiotropic effects on both inflammatory cells and airway structural cells, which are involved in asthma pathogenesis. We evaluated the effects of IL-9 blockade on chronic airway inflammation. METHODS: Acute airway inflammation was induced in Balb/c mice using aerosolized ovalbumin (OVA), whereas chronic asthma was induced by OVA exposure for 5 weeks with anti-IL-9 or isotype-matched antibody (Ab) treatment during the OVA challenge. Inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted and lung tissues were stained to detect cellular infiltration, mucus deposition, and collagen accumulation. The levels of interferon (IFN)-gamma, IL-4, IL-5, IL-9, IL-17, and immunoglobulin E (IgE) in BALF were measured using enzyme linked immunosorbent assays, and profiles of inflammatory cells and subsets of T helper (Th) cells were analyzed using flow cytometry. RESULTS: IL-9, IL-17, and IFN-gamma levels were significantly increased in the chronic group compared to the acute asthma group. However, the number of IL-9-positive cells was not affected, with a decrease in Th17 cells in OVA-challenged caspase-1 knockout mice. Numbers of eosinophils, neutrophils, B cells, mast cells, and Th17 cells decreased after administration of anti-IL-9 Ab. Total IgE, IL-5, IL-9, and IL-17 levels were also lower in the anti-IL-9 group. CONCLUSIONS: Our results suggest that anti-IL-9 Ab treatment inhibits pulmonary infiltration of inflammatory cells and cytokine production, especially IL-17. These results provide a basis for the use of an anti-IL-9 Ab to combat IL-17-mediated airway inflammation.