Toll-like receptor 3 signaling contributes to the expression of a neutrophil chemoattractant, CXCL1 in human mesangial cells

作者：Imaizumi Tadaatsu; Aizawa Tomomi; Segawa Chihiro; Shimada Michiko; Tsuruga Kazushi; Kawaguchi Shogo; Matsumiya Tomoh; Yoshida Hidemi; Joh Kensuke; Tanaka Hiroshi^*

来源：Clinical and Experimental Nephrology, 2015, 19(5): 761-770.

DOI：10.1007/s10157-014-1060-4

• CXCL1
• Human mesangial cells
• IFN-beta
• Inflammatory renal diseases
• Lupus nephritis
• Psuedoviral immunity
• TLR3

Mesangial proinflammatory chemokine/cytokine expressions via innate immunity play a pivotal role in the pathogenesis of glomerulonephritis. CXCL1/GRO alpha is a strong neutrophil chemoattractant cytokine and reportedly plays an important role in regional inflammatory reactions. However, detailed signaling of mesangial CXCL1 expression induced by viral or "pseudoviral" immunity remains to be determined.
We treated normal human mesangial cells (MCs) in culture with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, and analyzed the expression of CXCL1 by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative RT-PCR and enzyme-linked immunosorbent assay. To elucidate the poly IC-induced signaling pathway for CXCL1 expression, we subjected the cells to RNA interference against Toll-like receptor (TLR) 3, retinoic acid-inducible gene-I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), interferon (IFN)-beta, nuclear factor (NF)-kappa B p65 and IFN regulatory factor (IRF) 3. We also conducted an immunofluorescence study to examine mesangial CXCL1 expression in biopsy specimens from patients with lupus nephritis (LN) and IgA nephropathy (IgAN).
We found that activation of TLR3 signaling could induce the expression of CXCL1 in MCs. NF-kappa B, IRF3 and IFN-beta, but neither RIG-I nor MDA5, were found to be involved in mesangial CXCL1 expression in this setting. Induction of CXCL1 by poly IC was inhibited by pretreatment of cells with dexamethasone. Intense glomerular CXCL1 expression was observed in biopsy specimens from patients with LN, whereas only a trace staining occurred in specimens from patients with IgAN.
TLR3 signaling also contributes to the CXCL1 expression in MCs. These observations further support the implication of viral and "pseudoviral" immunity in the pathogenesis of inflammatory renal diseases, especially in LN.

• 出版日期2015-10