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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.
Conflict of interest
None.
Statement of ethics
This study was not involved human subjects which required ethical approval.