Chloroquine attenuates TLR3/IFN-β signaling in cultured normal human mesangial cells: A possible protective effect against renal damage in lupus nephritis. Issue 6 (2nd November 2017)

• Record Type: Journal Article
• Authors: Imaizumi, Tadaatsu; Hayakari, Ryo; Matsumiya, Tomoh; Yoshida, Hidemi; Tsuruga, Kazushi; Watanabe, Shojiro; Kawaguchi, Shogo; Tanaka, Hiroshi
• Is Part Of: Modern rheumatology. Volume 27:Issue 6(2017)
• Page Start: 1004
• Page End: 1009
• Publication Date: 2017-11-02
• Subjects: Chloroquine -- lupus nephritis -- mesangial cells -- NF-κB -- TLR3; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1080/14397595.2017.1289646
• Languages: English
• ISSNs: 1439-7595

Abstract

Abstract: Background: Chloroquine has been reported to protect against renal damage in lupus nephritis (LN); however, its detailed mechanism in glomerular inflammation remains unclear. Upregulation of the type-I interferon (IFN) system plays a pivotal role in LN pathogenesis, therefore, we examined whether chloroquine inhibits toll-like receptor 3 (TLR3)/IFN-β signaling in cultured normal human mesangial cells (MCs). Methods: We examined chloroquine effect on the representative TLR3/IFN-β-signaling axis, TLR3/IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5 in MCs treated with polyinosinic-polycytidylic acid (poly IC), a synthetic viral dsRNA analog and analyzed the expression of these molecules using reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Furthermore, we subjected MCs to RNA interference against NF-κB p65. Results: Pretreatment of cells with chloroquine attenuated IFN-β, RIG-I and CCL5 expression and phosphorylation of STAT1 induced by poly IC, but not IFN-β-induced phosphorylation of STAT1 and RIG-I expression induced by IFN-β. Knockdown of p65 inhibited the poly IC-induced IFN-β expression, and chloroquine pretreatment decreased the nuclear poly IC-induced translocation of NF-κB p65 in MCs. Conclusion: These results suggest that chloroquine attenuates mesangial TLR3 signaling in the early phase of NF-κB activation. Considering that TLRs/type-I IFNs signaling is implicated in LN pathogenesis, our results may further support regional renoprotective effects of chloroquine in treating LN.