The mechanistic role of Hydroxychloroquine on NFAT signaling in CD154 expression on CD4+ T lymphocyte of systemic lupus erythematosus

• Main Authors: TUNG, CHIEN-HSUEH, 童建學
• Other Authors: WU, SHU-FEN
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/c3mpth

博士 === 國立中正大學 === 生命科學系分子生物研究所 === 106 === Background: Over-expression of membranous CD154 in T lymphocytes has been previously found in systemic lupus erythematosus (SLE). As hydroxychloroquine (HCQ) has been frequently used in the treatment of lupus, we sought to identify the effects of HCQ on CD154 and a possibly regulatory mechanism. Methods: CD4+ T cells were isolated from the blood of lupus patients. After stimulated with ionomycin or IL-15 and pre-treated with various concentrations of HCQ, expression of membranous CD154, NFAT and STAT5 signaling were assessed. Results: HCQ pre-treatment had significant dose-dependent suppressive effects on membranous CD154 expression in ionomycin-activated T cells from lupus patients. Furthermore, HCQ inhibited intracellular sustained calcium storage release, and attenuated the nuclear translocation of NFATc2 and the expression of NFATc1. However, the expression of CD154 through IL-15 mediated STAT5 signaling was not inhibited by HCQ treatment. Conclusions: HCQ inhibited NFAT signaling in activated T cells and blocked the expression of membranous CD154, but not STAT5 signaling. These findings provide one of the mechanistic insights into SLE in HCQ treatment.