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

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)-1β 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-1β, 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-1β 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-1β 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.