ABSTRACT
Objective:To analyze the role of acetylsalicylic acid (ASA) in immunomodulation of mesenchymal stem cells derived from gingiva (GMSCs),and to explore the role of ASA in enhancing the immumomodulation of GMSCs and the capacity of GMSCs to treat immune disorders and the underlying mechanism.Methods:Flow cytometry analysis were used to analyze the role of ASA in the expression of stem cells surface markers CD146,CD105,CD90,CD34 and CD45 in GMSCs,and the GMSCs proliferation was analyzed by 5-bromo-2-deoxyuridine (BrdU) staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.The GMSCs and T cells co-culture system was established to analyze the role of ASA in immunomodulation of GMSCs by measuring T cell apoptosis using flow cytometry analysis and inflammatory cytokines using enzyme linked immunosorbent assay (ELISA).Further more,the dextran sulfate sodium (DSS) induced colitis mouse model was established and the mouse body weight,disease activity score,histological index and pathological change of colons were analyzed after GMSC infusion.Results:The proliferation of GMSCs and the expressions of CD105,CD146 in GMSCs were increased after ASA treatment.In the GMSCs and T cells co-culture system,GMSCs induced T cells apoptosis and inhibited interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) secretion by T cells,which were enhanced by ASA treatment.In vivo,GMSCs infusion could ameliorate DSS-induced colitis,including inhibited DSS-induced mouse body weight loss,decreased disease activity score and histological index,and decreased inflammation cells infiltration in colons,as shown by hematoxylin-eosin (HE) staining.Moreover,the therapeutic effects of GMSC infusion on DSS-induced colitis could be enhanced by ASA treatment.Mechanically,ASA treatment increased FasL expression of Fas/ FasL death pathway in GMSCs to induce T cells apoptosis.Conclusion:ASA enhanced immunomodulation of GMSCs and increased the capacity of GMSCs to ameliorate DSS-induced colitis in mice.
ABSTRACT
<p><b>BACKGROUND</b>Takayasu arteritis (TA) is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population.</p><p><b>METHODS</b>Four single nucleotide polymorphisms (SNPs) those locate in the IL12B region (rs56167332), the MLX region (rs665268), the FCGR2A/FCGR3A locus (rs10919543), and the HLA-B/MICA locus (rs12524487), associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants.</p><p><b>RESULTS</b>Among the four SNPs, rs10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs10919543 at the FCGR2A/FCGR3A locus is a high risk factor (odds ratio [OR] = 6.532, 95% confidence interval [CI] = 2.402 - 17.763, P < 0.001) for TA. Among TA patients, the level of eosinophil granulocytes (Eos) in the peripheral blood was observed to be higher in the GG group of rs10919543 (n = 23, Eos = 0.11 [0.08, 0.17] ×109/L) than the GA + AA group (n = 100, Eos = 0.08 [0.05, 0.13] ×109/L, P = 0.028). No correlation between the genotypes of the other three SNPs and TA patients was observed.</p><p><b>CONCLUSIONS</b>Our findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA.</p>