RANTES, MCP-1, and SDF-1β levels in healthy people and AIDS patients: a comparative analysis / 中国感染控制杂志

Objective To evaluate the differences of serum RANTES(regulated on activation, normal T cell expressed and secreted), MCP-1 (monocyte chemoattractant protein), and SDF-1β (stromal cell-derived factor-1β) in patients with acquired immunodeficiency syndrome (AIDS) and healthy people.Methods 38 AIDS patients who were admitted to a hospital between January 2010 and January 2015 were as AIDS groups, 38 healthy persons were as a healthy group, serum levels of RANTES, MCP-1, and SDF-1β in two groups were detected, and the subgroup analysis was carried out according to the viral load.Results Serum levels of RANTES, MCP-1, and SDF-1β in AIDS group were (1 392.55±227.69)pg/mL,(450.91±103.04)pg/mL, and(104.82±22.52)pg/mL respectively,all were significantly higher than those in healthy group([120.58±55.87] pg/mL, [74.25±33.62] pg/mL, and [39.04±11.43]pg/mL respectively)(all P<0.05).Among AIDS patients with HIV viral load 4≤Log(VL)<5 and Log(VL)≥5, serum RANTES were (1 470.34±155.01)pg/mL and (1 408.29±181.54)pg/mL respectively,which were both significantly higher than patients with HIV viral load Log(VL)<4([1 183.12±174.54]pg/mL);serum MCP-1 and SDF-1β levels in AIDS patients with HIV viral load 4≤Log (VL)<5 were (537.93±89.32)and(149.31±18.05)pg/mL respectively,which were significantly higher than patients with HIV viral load Log(VL)≥5([410.26±80.57] pg/mL, [81.53±20.31]pg/mL respectively) and HIV viral load Log(VL)<4([381.71±77.26] pg/mL, [72.90±21.62]pg/mL respectively), differences were both statistically significant(both P<0.05).Conclusion Serum levels of RANTES, MCP-1, and SDF-1β are significantly increased in AIDS patients, which are related to the level of viral load.

Association of serum chemokine levels with cognitive dysfunction in newly diagnosed T2DM patients / 医学研究生学报

Objective Decline in cognitive function caused by diabetes has become a research hotpots.The article aims to explore the relationship between serums regulated upon activation normal T cell expressed and secreted(RANTES) and cognitive dysfunction of newly diognosed T2DM patients, and provide a new way of prevention and treatment for newly diagnosed T2DM patients with cognitive dysfunction.Methods We retrospectively analyzed the general information and clinical biochemical indexes of the 123 patients who were first diagnosed of T2DM from March 2015 to September 2016 in Tangshan Worker''s Hospital.The levels of serum RANTES were measured by enzyme-linked immunosorbent assay (ELISA), and the cognitive function of all patients was assessed by Mini-mental State Examinatlon(MMSE)and Repeatable Battery for the Assessment of Neuropsyehologic Status(RBANS).Finally, newly diognosed T2DM patients were divided into T2DM non-cognitive disorder group and T2DM cognitive disorder group according to the MMSE score.We analyzed whether there are differences among general information,serum RANTES level and RBANS cognitive function score of two group patients.The correlations of RANTES with general information and cognitive scores were analyzed by single factor correlation and multiple stepwise regression analysis.Results ①The level of serum RANTESin T2DM cognitive disorder group[(2.62±0.37)mmol/L] was significantly higher compared to that in T2DM noncognitive disorder group[(2.29±0.36)mmol/L], and there was significant difference(P<0.001).②The instant memory,visual span,attention,delayed memory score and RBANS score of T2DM cognitive disorder group were(70.90±14.71)、(92.90±15.50)、(87.80±16.45)、(88.02±14.28)、(82.92±11.07), which were significant declined compared to those of T2DM non-cognitive disorder group [(85.28±13.97),(104.18±12.69),(101.51±12.94),(96.42±10.30),(95.84±9.94)], and there was significant difference (P≤0.05).There was no statistically significant difference between the two groups′ verbal function score [(96.08±7.87),(99.31±9.83)] (P=0.056).③The RANTES was negatively correlated with the total score of instant memory, visual span, verbal function, delayed memory score and RBANS score in T2DM patients(the valuue of r were-3.48、-2.35、-2.01、-3.02、-4.17).Conclusion There was a significant correlation between serum RANTES level and cognitive dysfunction, and elevated serum RANTES level could be used as an important indicator for monitoring newly diognosed T2DM patients with cognitive dysfunction.

Inhibition of the Inflammatory Response and Its Mechanism by Hydrochloric Acid Chlorobenzene Sulperzon (HACS) in Astrocytes / 中国药学杂志

OBJECTIVE: To evaluate the inhibitory effects and mechanism of Hydrochloric acid chlorobenzene sulperzon (HACS) on neuronal inflammation were studied in order to evaluate possible application of it in AD therapy. METHODS: The release of NO (nitric oxide) by astrocyte was detected by Griess methods and the chemotaxis of mouse macrophage was detected by Boyden chemotaxis chamber. The cell viability was detected by MTT assay. The content of IL-6 and RANTES (T cell expressed and presumably secreted)was determined by ELISA. The expression of mRNA of IL6 and RANTES was detected by RT-PCR. The intracelluar Ca2+ was detected by confocal microscope. RESULTS: HACS efficiently decreased the release of NO from astrocyte stimulated by LPS (1 μg·mL-1), chemotaxis of mouse macrophage stimulated by PAF (5×10-8 mol·L-1), expression of IL-6 and regulated upon activation of RANTES in U251 cells induced by IL-1β (50 ng·mL-1). In addition, HACS significantly inhibited the increase of intracellular Ca2+ in U251 cells induced by Aβ1-42(50 μg·mL-1)/sodium glutamate(100 μmol·L-1)or IL-1β(50 ng·mL-1). CONCLUSION: HACS efficiently inhibites the activation of astrocyte by regulation of intracelluar Ca2+inhibition of chemotaxis and decrease of inflammatory cytokines. Especially, the inhibition of RANTES and intracelluar Ca2+ induced by inflammatory mediators by HACS is firstly reported in this study.

Expression of Eotaxin and RANTES in Nasal Polyps versus Healthy Nasal Mucosa, a Case Control Study.

Aims: To investigate the levels of the chemokines; eotaxin and RANTES in chronic rhinosinusitsis with nasal polyposis in comparison to their levels in control healthy nasal mucosa to evaluate if they might play a role in pathogenesis. Study Design: We performed a prospective case control study. Place of Study and Duration: This study was performed in Otorhinolarngology Department Mansoura University Hospitals, Egypt. Methodology: It included 60 patients suffering from chronic rhinosinsuitis with nasal polyposis, in addition to 20 subjects that were included as control. Nasal tissue samples were collected from all cases and control to estimate the levels of eotaxin and RANTES by ELISA. Results: The estimated levels of eotaxin and RANTES in nasal polyps were higher than their measured levels in healthy nasal mucosa from control group and the results were statistically significant. Conclusion: The measured levels of eotaxin and RANTES suggest that they may have a role in pathogenesis of chronic rhinosinusitis with nasal polyposis and can be considered as a good target for medical therapy until supported by further studies.

Induction of long-term heart survival after secondary transplantation by anti-RANTES monoclonal antibody combined with ciclosporin in mouse models / 器官移植

Objective To evaluate the effect of anti-RANTES monoclonal antibody in combination with ciclosporin (CsA)upon inhibiting the rejection response during secondary heart transplantation in mouse models. Methods BALB/c mouse models were used as the donors and C57BL/6 mice were utilized to establish secondary heart transplantation recipient models. The animals were randomly divided into the control (physiological saline,n =6 ),A (anti-RANTES monoclonal antibody treatment,n =6 ),B (CsA treatment,n =6 ) and C groups (anti-RANTES monoclonal antibody combined with CsA treatment,n=6). The survival time of heart after secondary transplantation was observed. The degree of acute heart rejection was assessed by histopathological analysis. The relative expression levels of RANTES,interleukin(IL)-2,IL-1 0,interferon(IFN)-γand transcription growth factor(TGF)-βmessenger ribonucleic acid (mRNA)in the heart grafts were quantitatively measured by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The serum levels of RANTES,IFN-γ,IL-2,IL-1 0 and TGF-βwere detected by enzyme-linked immune absorbent assay (ELISA). Results The heart grafts of all mice survived after secondary cardiac transplantation. Compared with the control group,the survival time of hearts in group A,B and C was significantly prolonged (all P<0. 01 ). Pathological staining revealed that the quantity of infiltrated inflammatory cells in group C was significantly decreased than those in the other groups. The expression levels of heart RANTES,IFN-γand IL-2 mRNA in group C were significantly down-regulated, whereas the expression levels of IL-1 0 and TGF-βmRNA were considerably up-regulated compared with those in the other three groups (all P<0. 05). The serum levels of RANTES,IL-2 and IFN-γin group C were significantly down-regulated, whereas the serum contents of IL-1 0 and TGF-βwere considerably up-regulated compared with those in the other three groups (all P<0. 05 ). Conclusions Combined application of anti-RANTES monoclonal antibody and CsA can effectively induce the immune tolerance to secondary cardiac transplantation and prolong the survival time of the cardiac grafts in mouse models.

Role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism

Our aim was to investigate the role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism. Coronary angiography and intravascular ultrasound (IVUS) were performed in 60 stable angina pectoris (SAP) patients and 60 unstable angina pectoris (UAP) patients. The chemotactic activity of monocytes in the 2 groups of patients was examined in Transwell chambers. High-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), regulated on activation in normal T-cell expressed and secreted (RANTES), and fractalkine in serum were examined with ELISA kits, and expression of MCP-1, RANTES, and fractalkine mRNA was examined with real-time PCR. In the SAP group, 92 plaques were detected with IVUS. In the UAP group, 96 plaques were detected with IVUS. The plaques in the UAP group were mainly lipid 51.04% (49/96) and the plaques in the SAP group were mainly fibrous 52.17% (48/92). Compared with the SAP group, the plaque burden and vascular remodeling index in the UAP group were significantly greater than in the SAP group (P<0.01). Chemotactic activity and the number of mobile monocytes in the UAP group were significantly greater than in the SAP group (P<0.01). Concentrations of hs-CRP, MCP-1, RANTES, and fractalkine in the serum of the UAP group were significantly higher than in the serum of the SAP group (P<0.05 or P<0.01), and expression of MCP-1, RANTES, and fractalkine mRNA was significantly higher than in the SAP group (P<0.05). MCP-1, RANTES, and fractalkine probably promote instability of coronary atherosclerotic plaque.

Expression of nuclear factor kappaB, MCP-1 and RANTES concentration in peritoneal fluid in women with endometriosis / 实用医学杂志

Objective To compare the concentration of nuclear factor-kappa B (NF-κB), MCP-1 and RANTES in peritoneal fluid in women with endometriosis and normal peritonal fluid ,To explore the relationship between these cytokines with pathogenesis of endometriosis. Methods There were 2 groups:the endometriosis group and the control group.Double-antibody sandwich ABC-ELISA technique was adopted for determinating concentration of NF-кB、MCP-1 and RANTES in peritoneal fluid. Results Peritoneal fluid level of NF-κB MCP-1 and RANTES in endometriosis patients was higher than the control group (P < 0.05). NF-κB and MCP-1, NF-κB and RANTES expressed positive correlation by linear correlation analysis in both EMs group and control group , correlation coefficients were 0.385, 0.569(EMs group), 0.474, 0.388(P < 0.05). Conclusions NF-кB、MCP-1 and RANTES are mutual affection and promote endometriosis in the pathogenesis.

Predictive Value of Conjointly Examined IL-1ra, TNF-R I, TNF-R II, and RANTES in Patients with Primary Glomerulonephritis

Interleukin-1 receptor antagonist (IL-1ra), tumor necrosis factor soluble receptors (sTNF-R) type I and II, and regulated upon activation, normal T-cell expressed and secreted (RANTES) play an important role in the modulation of primary glomerulonephritis (GN) course. The aim of the study was to assess whether pre-treatment measurements of IL-1ra, sTNF-R, and RANTES assessed conjointly may be useful as predicting factors in patients with GN. In 84 patients (45 males and 39 female) serum concentration (pg/mL) and urinary excretion (pg/mgCr) of cytokines were measured. After 12 months of therapy with steroids and cyclophosphamide the patients were divided into two subgroups: Responders (R) and Non-Responders (NR) according to the treatment results. The urinary IL-1ra, TNF-RI and RII were significantly higher in R than NR (1,732 vs 646 with P < 0.001, 13.1 vs 6.3 with P = 0.005, and 33.6 vs 14.4 with P = 0.012). The urinary RANTES excretion was increased in NR (79.6 vs 28.5; P < 0.001). The multivariable analysis showed that if conjointly assessed, only urinary IL-1ra, TNF-R I and R II, RANTES with 85% probability pointed the feature remission (R). In conclusion, the urinary excretion of IL-1ra, TNF-R I and R II, and RANTES examined conjointly are effective in predicting favorable response to immunosuppressive treatment in patients with GN.

The Evaluation and Significance of RANTES in Serum and Peritoneal Fluid in Patients with Endometriosis / 天津医药

Objective To investigate the role and clinical significance of RANTES in endometriosis (EM). Methods The serum level of RANTES was examined by ELISA in 50 patients with endometriosis (EM group), 32 patients with benign ovarian neoplasms (disease control group) and 30 normal control women (normal control group). The level of RANTES in peritoneal fluid was examined in EM group and disease control group. Results The serum level of RANTES was significantly higher in EM group (108.73±60.69) ng/L than that of disease control group (31.26±20.33) ng/L and normal control group (29.77 ± 11.58) ng/L (P＜0.05). The level of RANTES in peritoneal fluid was significantly higher in EM group (726.31 ± 259.83) ng/L than that of disease control group (116.19 ± 81.64) ng/L (P＜0.05). The levels of RANTES in serum and peritoneal fluid in EM group were positively correlated with clinical stage respectively (rs=0.501 and 0.562,P＜0.01). The level of RANTES in peritoneal fluid in EM group was positively correlated with dysmenorrhea score (rs=0.527,P＜0.01). The serum level of RANTES was positively correlated with the level of RANTES in peritoneal fluid in EM group (rs=0.363, P＜0.05). The levels of RANTES in serum and peritoneal fluid were positively correlated with inflammatory response degree in endometriotic tissues in EM group (rs=0.326 and 0.391,P＜0.05 or P＜0.01).Conclusion Detection of the serum level of RANTES by ELISA may be one of parameters for diagnosis of endometriosis.

Asociación entre los valores de Rantes y la clínica en pacientes con rinitis alérgica / Association between rantes values and the clinical aspect in patients with allergic rhinitis

Objetivo: Determinar los valores de Rantes, después de la exposición a ácaros, para evaluar su asociación con la escala ARIA, en el grupo de pacientes seleccionado. Diseño: Estudio de corte transversal. Materiales y métodos: Se incluyeron 17 pacientes que consultaron por rinitis alérgica en el Hospital de La Samaritana entre el 1 de julio del 2010 y el 1 julio del 2011, y que cumplieron los criterios de selección, de los cuales se obtuvieron 34 muestras de lavados nasales posteriores a provocación intranasal con ácaros. Resultados: Los pacientes mostraron mayor tendencia a pertenecer al grupo de síntomas de mayor severidad y frecuencia según la escala ARIA. Los valores de Rantes encontrados en lavados nasales tuvieron un promedio de 8,1 pg/ml (+/– 19DS). Conclusión: Se encontró una positividad en los valores de la citoquina CCL5 en los lavados nasales del 20% de los pacientes. El coeficiente de correlación obtenido muestra una asociación débil.

Objective: Determine the values of Rantes, after exposure to mites, to evaluate its association with ARIA scale in the group of selected patients. Design: Cross sectional survey. Materials and Methods: We included 17 patients presenting with allergic rhinitis at the Samaritan Hospital between July 1, 2010 and July 1, 2011, and met the selection criteria, of which 34 samples were obtained from nasal washes after intranasal challenge with mites. Results: Patients showed a greater tendency to belong to the group of symptoms of greater severity and frequency according to the ARIA scale. Rantes values found in nasal washes had an average of 8.1 pg/ml (+/– 19DS). Conclusions: Positivity was found in the values of the cytokine CCL5 in nasal washes of 20% of patients. The correlation coefficient shows a weak association.

Comparison of Serum Interleukin-8 and Regulated on Activation in Normal T-Cell Expressed and Secreted Levels in Atopic and Non-Atopic Children with Lower Respiratory Tract Infections / 소아알레르기및호흡기학회지

PURPOSE: Several studies have shown that viral respiratory infections induce more severe respiratory symptoms in atopic patients than in normal subjects. We attempted to investigate if there is any difference in the viral etiology, clinical manifestations, production of interleukin (IL)-8, and regulated on activation in normal T-cell expressed and secreted (RANTES) between atopic and non-atopic subjects with lower respiratory infections. METHODS: Sera and nasopharyngeal aspirates (NPA) were collected from 97 children with lower respiratory infections who were admitted to the pediatric ward. Seventy-one children were classified as atopic subjects. We detected respiratory viruses with multiplex reverse transcriptase-polymerase chain reaction in NPA and measured total immunoglobulin E (IgE) and specific IgE in sera. IL-8 and RANTES levels measured in sera by enzyme-linked immunosorbent assay, etiology, and clinical manifestations were compared between atopic and non-atopic subjects. Atopic patients were defined as having elevated specific IgE to more than one allergen or age-matched, high serum total IgE levels. RESULTS: Both serum IL-8 and RANTES levels were significantly higher in atopic than in non-atopic patients. There was no significant difference in viral etiology and clinical diagnosis between the two groups. The frequency of wheezing was higher in atopic than in non-atopic patients. CONCLUSION: Our study showed that both serum IL-8 and RANTES levels and the frequency of wheezing were significantly higher in atopic than in non-atopic patients. That suggests that chemokine responses to viral respiratory infection may be different between atopic and non-atopic patients and may be associated with a difference in clinical manifestation, such as wheezing, between the two groups. However, further prospective large-scaled studies are required to clarify our conclusion.

Effect of respiratory syncytial virus infection on regulated on activation, normal T-cells expressed and secreted production in a murine model of asthma / 소아과

PURPOSE: Synthesis of regulated on activation, normal T-cells expressed and secreted (RANTES) in the airway has previously been shown to be elevated after respiratory syncytial virus (RSV) infection. However, since few studies have examined whether RSV-infected asthma patients express a higher level of RANTES than do normal individuals, we used a murine model of asthma to address this question. METHODS: We prepared Dermatophagoides farinae-sensitized mice as an asthma model, and then infected them with RSV and analyzed the changes in airway responsiveness and the cell populations and cytokine levels of bronchoalveolar lavage fluid. RESULTS: RANTES synthesis increased in response to RSV infection in both control mice and in asthma model (D. farinae) mice. However, there was no significant difference in the amount of RANTES produced following RSV infection between control and D. farinae mice. RSV infection affected neither interferon-gammasynthesis nor airway responsiveness in either control or D. farinae mice. CONCLUSION: RSV infection did not induce more RANTES in a murine model of asthma than in control mice.

Effect of respiratory syncytial virus infection on regulated on activation, normal T-cells expressed and secreted production in a murine model of asthma / 소아과

PURPOSE: Synthesis of regulated on activation, normal T-cells expressed and secreted (RANTES) in the airway has previously been shown to be elevated after respiratory syncytial virus (RSV) infection. However, since few studies have examined whether RSV-infected asthma patients express a higher level of RANTES than do normal individuals, we used a murine model of asthma to address this question. METHODS: We prepared Dermatophagoides farinae-sensitized mice as an asthma model, and then infected them with RSV and analyzed the changes in airway responsiveness and the cell populations and cytokine levels of bronchoalveolar lavage fluid. RESULTS: RANTES synthesis increased in response to RSV infection in both control mice and in asthma model (D. farinae) mice. However, there was no significant difference in the amount of RANTES produced following RSV infection between control and D. farinae mice. RSV infection affected neither interferon-gammasynthesis nor airway responsiveness in either control or D. farinae mice. CONCLUSION: RSV infection did not induce more RANTES in a murine model of asthma than in control mice.

Analysis of CCL5 Concentration in Tears of Dry Eye Patients

PURPOSE: To investigate the expression of CCL5/RANTES (regulated upon activation, normal T cell expressed and secreted) in the tears of dry eye patients. METHODS: Forty patients with dry eye (15 Sjogren's and 25 non-Sjogren's syndrome patients) and ten control subjects were recruited for the present study. The concentration of RANTES in tears was measured using an enzyme-linked immunosorbent assay. The correlations between RANTES level, tear film and ocular surface parameters, including tear film break-up time, basal tear secretion, tear clearance rate, corneal sensation, keratoepitheliopathy, and conjunctival goblet cell density, were analyzed in patients with dry eye syndrome. RESULTS: The concentrations of RANTES were 435.46 +/- 104.45 pg/ml in Sjogren's syndrome patients, 257.42 +/- 46.72 pg/ml in non-Sjogren's syndrome patients, and 97.53 +/- 29.15 pg/ml in the control patients (p < 0.01). The levels correlated significantly with basal tear secretion, tear clearance rate, keratoepitheliopathy, and goblet cell density (p < 0.05). CONCLUSIONS: CCL5/RANTES level increases in the tears of dry eye patients and correlates with various tear film and ocular surface parameters.

Infliximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naive Patients with Crohn's Disease

BACKGROUND/AIMS: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-alpha has efficacy in treating Crohn's disease (CD). However, knowledge of the potential effects of IFX on patients' immune profiles is lacking. The purpose of this study was to reveal the immunological effects of IFX. METHODS: Twenty-two patients with a CD activity index (CDAI) of 194.2+/-92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their first IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. RESULTS: CDAI significantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-beta1 (p<0.01), and 'regulated on activation, normal T cell expressed and secreted' (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-alpha (p<0.04), IL-6 (p<0.03), interferon (IFN)-gamma (p<0.04), IFN-gamma-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage inflammatory protein-1beta (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-gamma)/Th2 (IL-4) ratio (p<0.03). CONCLUSIONS: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naive Th0 lymphocytes to Treg. This knowledge should have clinical relevance.

Analysis of inhibitory effect of CCR5 on dihydrofolate reductase expression by two-dimensional electrophoresis / 第二军医大学学报

Objective: To identify the differentially expressed proteins after activation of CCR5 by its ligand using two-dimensional electrophoresis. Methods: The HEK-293 cells stably expressing CCR5 were constructed. The global protein analysis in 293-CCR5 stables and mock cells was performed after treatment with RANTES. After analysis with the PDQuest image software, the differential spots were identified by MOLDI-TOF MS/MS. RT-PCR was performed to further analyze the changes at mRNA level. Results: Flow cytometry revealed that HEK-293 cells stably expressed CCR5. In this study, we analyzed the proteomic results to reveal the proteins which were significantly modulated by the activation of CCR5 with RANTES. Expression of dihydrofolate reductase was found in HEK-293 cells after RANTES treatment, which was confirmed by RT-PCR at the mRNA level. Conclusion: This proteomic study suggests that CCR5 activated by its ligand RANTES inhibits the expression of dihydrofolate reductase.

Construction of adenovirus vector harboring RANTES regulated by oxygen-dependent degradation domain and its chemoattractant activity in vitro / 第二军医大学学报

Objective: To construct an adenovirus vector harboring the human RANTES gene regulated by oxygen-dependent degradation domain (ODD) and to observe its chemoattractant activity in vitro. Methods: The human RANTES gene was fused with ODD by PCR and the recombinant adenovirus was used to construct SG511-CCL5-ODD with the Gateway System. Viral replication experiments were performed to evaluate the selective replication ability of SG511-CCL5-ODD. The expression of RANTES protein was determined by ELISA under normal and hypoxia condition. Chemotactic test was used to analyze the chemoattractant ability of the expressed RANTES in liver cancer cells. Results: A recombinant adenovirus SG511-CCL5-ODD was constructed successfully. Cells infected with the recombinant virus expressed RANTES selectively. The expression of RANTES protein in the transfected liver cancer cells was higher under hypoxia condition than under normal condition (P<0.05), indicating ODD can effectively regulate RANTES protein expression. Chemotactic test showed that liver cancer cell infected with SG511-CCL5-ODD had the ability to recruit NK92 cells. Conclusion: Recombinant vector SG511-CCL5-ODD can effectively infect liver cancer cell line HepG2 and Hep3B, and can express RANTES protein under the regulation of ODD, demonstrating a chemoattractant activity in vitro.

Expression of NF-κB and regulated upon activation normal T cell expressed and secreted chemokine in experimental abscending aortic aneurysm rat model / 解剖学报

Objective To investigate the expression of nuclear factor kappaB(NF-κB) and regulated upon activation normal T cell expressed and secreted chemokine(RANTES) during the formatiom of ascending aortic aneurysm. Methods Forty Wistar rats were randomly divided into the control group(n=20) and the experimental group(n=20).The rat models were made by ligating the ascending aorta. The ascending aortas were taken after ligation for 3months. Immunohistochemistry staining was performed to detect the protein expression of NF-κB and RANTES. The expression of NF-κB and RANTES mRNA were detected by RT-PCR. Results Immunohistochemisry staining results showed NF-κB and RANTES expression significantly increased in aneurysm, while there was a little positive staining in the control group. RT-PCR results indicated that the expression levels of NF-κB and RANTES in the aneurysm were stonger than that of the control group. The expression of NF-κB and RANTES mRNA were remarkably correlated. Conclusion The expression of NF-κB and RANTES in ascendin aortic aneurysm are stronger than that in the control. NF-κB and RANTES may contribute to the pathogenesis of the ascending aortic aneurysm.

Association Study between CCL-2 and CCL-5 Polymorphisms and Clinicopathological Characteristics of Childhood IgA Nephropathy

PURPOSE: Previous studies have suggested that Chemokine (C-C motif) ligand-2 (CCL-2; also known as MCP-1) and CCL-5 (also known as RANTES) are possibly associated with the pathogenesis of various inflammatory and non-inflammatory renal diseases. The present study was conducted to investigate association of polymorphisms of CCL-2 and CCL-5 genes with childhood IgA nephropathy (IgAN). METHODS: The authors analyzed six single nucleotide polymorphisms (SNPs) of CCL-2 and CCL-5 in 196 pediatric IgAN patients and in 285 healthy controls. We compared variations in SNPs between two several sets of IgAN subgroups, allocated by presence of proteinuria (>4 mg/m2/hour), podocyte foot process effacement, and pathologically advanced disease markers, such as interstitial fibrosis, tubular atrophy, or global sclerosis. RESULTS: Genotypic data of IgAN patients and controls showed no significant SNP frequency difference in both of of CCL-2 and CCL-5. Even though two linkage disequilibrium blocks were formed, there was no significance in the haplotype analysis. In the patient subgroup analysis, no SNP of CCL-2 and CCL-5 was found to be associated with the presence of proteinuria, podocyte foot process effacement, and pathologically advanced disease markers. CONCLUSION: Our data indicate that no association exists between CCL-2 and CCL-5 SNPs and childhood IgAN susceptibility, and presence of proteinuria, podocyte foot process effacement, and pathologic progression of IgAN.

Peptidoglycan modulation of chemokine production in normal human epidermal kerafinocytes and the role of Toll-like receptor 2 in this process / 中华皮肤科杂志

Objective To investigate the effect ofpeptidoglycan from Staphylococcus aureus on the release of several chemokines including intedeukin 8 (IL-8), regulated upon activation, normal T cell expressed and secreted (RANTES), macrophage-derived chemokine (MDC) by normal human epidermal keratinocytes (KCs) and the role of Toll-like receptor 2 (TLR2) in this process. Methods KCs were derived from the foreskin of a healthy boy and propagated. After 2 - 4 passages, KCs were collected and treated with various concentrations (3, 10, 30 and 100 mg/L) of peptidoglycan for 24 hours or with peptidoglycan of 100 mg/L for varying durations (3, 6, 12, 36 hours). A fi'action of KCs were pretreated with functional grade purified anti-TLR2 monoclonal antibody before the treatment with peptidoglycan of 100 mg/L. After additional 12-hour culture following the treatment, enzyme linked immunosorbent assay was used to detect the level of IL-8, RANTES and MDC in culture supernatants of KCs. Results KCs spontaneously released IL-8 and RANTES. Peptidoglycan increased the production of IL-8 but decreased that of RANTES by KCs. The levels of IL-8 were 209.96 ± 10.31 ng/L, 250.28 ± 9.52 ng/L, 285.11 ± 10.28 ng/L, 359.40 ± 6.93 ng/L in KCs treated with peptidoglycan of 3, 10, 30, 100 mg/L, respectively, compared to 135.41 ± 14.37 ng/L in untreated KCs (all P < 0.05). On the contrary, a significant decrement was seen in the secretion of RANTES by KCs treated with peptidoglycan of 10, 30, 100 mg/L compared with untreated KCs (110.72 ± 8.51 ng/L, 90.50 ±2.45 ng/L, 49.89 ± 13.74 ng/L vs 149.94 ± 18.71 ng/L, all P < 0.05). The monoclonal antibody to TLR-2 could markedly suppress the promotion of IL-8 production by peptidoglycan, but had no obvious influence on the inhibition of RANTES production by peptidoglycan. MDC could not be detected in the culture super-natants of KCs with or without peptidoglycan stimulation. Conclusion Peptidoglycan could inhibit RANTES secretion but induce IL-8 production by KCs likely via TLR2.