Uric acid induces TLR4-dependent innate immune response but not HLA-DR and CD40 activation in renal proximal tubular epithelial cells

作者：Xiao, Jing; Zhang, Xiaoli; Han, Rui; Fu, Chensheng; Chen, Weijun; Ye, Zhibin^*

来源：International Journal of Clinical and Experimental Pathology, 2016, 9(2): 940-949.

• IL-1 beta
• NLRP3
• renal tubular epithelial cells
• TLR4
• uric acid

Hyperuricemia correlates with the development and progression of renal diseases. We have previously revealed that uric acid (UA) initiates immune responses through toll like receptors (TLR)4 dependent Nod-like receptor protein (NLRP) 3 inflammasome formation and interleukin (IL)-1 beta processing, as well as major human leukocyte antigen (HLA)-DR (surface receptor for major histocompatibility complex II) and CD40 over-expression in primary renal mesangial cell. In this study we aimed to verify whether UA also activates these immune responses in a renal tubular epithelial cell line HK-2 cells. Human proximal tubular cells HK-2 were incubated with UA and lipopolysaccharides (LPS). Gene and protein expression level of innate immune markers TLR2, TLR4, NLRP3 and IL-1 beta, adaptive immune markers HLA-DR and CD40, as well as intercellular adhesion molecule-1 (ICAM-1) were detected by RT-PCR, ELISA and Western blot, respectively. UA, like LPS, significantly enhanced the expression of TLR4, NLRP3, IL-1 beta and ICAM-1 but failed to increase TLR2 expression in HK-2 cells. Neither LPS nor UA could increase HLA-DR and CD40 expression in HK-2 cells. TLR4 inhibitor, TAK242, significantly blocked the UA-induced NLRP3 and IL-1 beta expression. Our findings suggest that UA induces TLR4 dependent innate immune response but not HLA-DR and CD 40 expression in renal proximal tubular cells.

• 出版日期2016
• 单位复旦大学