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作 者:Julien Pestel Maud Robert Sara Corbin Hubert Vidal Assia Eljaafari
机构地区:[1]INSERM U1060 CarMen,Batiment CENS-ELI,Centre Hospitalier Lyon Sud,Pierre Bénite 69310,France [2]Faculty of Medicine,UniversitéClaude Bernard Lyon 1,Batiment CENS-ELI,Centre Hospitalier Lyon Sud,Pierre Bénite 69310,France [3]Department of Surgery in Gastro-enterology,Edouard Herriot Hospital,Lyon 69003,France [4]Public Health Department,Hospices Civils de Lyon,1 quai des célestins Lyon 69002,France [5]DO-IT Research Team,Hospices Civils de Lyon,1 quai des célestins,Lyon 69002,France
出 处:《World Journal of Stem Cells》2020年第7期621-632,共12页世界干细胞杂志(英文版)(电子版)
摘 要:BACKGROUND Advanced glycation end products(AGE)are a marker of various diseases including diabetes,in which they participate to vascular damages such as retinopathy,nephropathy and coronaropathy.Besides those vascular complications,AGE are involved in altered metabolism in many tissues,including adipose tissue(AT)where they contribute to reduced glucose uptake and attenuation of insulin sensitivity.AGE are known to contribute to type 1 diabetes(T1D)through promotion of interleukin(IL)-17 secreting T helper(Th17)cells.AIM To investigate whether lean adipose-derived stem cells(ASC)could be able to induce IL-17A secretion,with the help of AGE.METHODS As we have recently demonstrated that ASC are involved in Th17 cell promotion when they are harvested from obese AT,we used the same co-culture model to measure the impact of glycated human serum albumin(G-HSA)on human lean ASC interacting with blood mononuclear cells.IL-17A and pro-inflammatory cytokine secretion were measured by ELISA.Receptor of AGE(RAGE)together with intercellular adhesion molecule 1(ICAM-1),human leukocyte Antigen(HLA)-DR,cluster of differentiation(CD)41,and CD62P surface expressions were measured by cytofluorometry.Anti-RAGE specific monoclonal antibody was added to co-cultures in order to evaluate the role of RAGE in IL-17A production.RESULTS Results showed that whereas 1%G-HSA only weakly potentiated the production of IL-17A by T cells interacting with ASC harvested from obese subjects,it markedly increased IL-17A,but also interferon gamma and tumor necrosis factor alpha production in the presence of ASC harvested from lean individuals.This was associated with increased expression of RAGE and HLA-DR molecule by cocultured cells.Moreover,RAGE blockade experiments demonstrated RAGE specific involvement in lean ASC-mediated Th-17 cell activation.Finally,platelet aggregation and ICAM-1,which are known to be induced by AGE,were not involved in these processes.CONCLUSION Thus,our results demonstrated that G-HSA potentiated lean ASC-mediated IL-17A pro
关 键 词:Interleukin 17 secreting T helper cells Lean adipose tissue Type 1 diabetes Advanced glycation end products Adipose-derived stem cells
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