Journal
MODERN RHEUMATOLOGY
Volume 30, Issue 6, Pages 1074-1081Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14397595.2019.1682768
Keywords
Chloroquine; fractalkine (CX3CL1); glomerular endothelial cells; lupus nephritis; Toll-like receptor 3
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Funding
- Japan Society for Promotion of Science (JSPS KAKENHI) [16K10055]
- Grants-in-Aid for Scientific Research [16K10055] Funding Source: KAKEN
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Background: Endothelial expression of membrane-bound fractalkine/CX3CL1 (Fkn) reportedly acts as a strong mediator of inflammation. Toll-like receptor 3 (TLR3) axes are thought to play some roles in the development of chronic glomerulonephritis (CGN) including lupus nephritis (LN). However, detailed mechanism of TLR3-mediated Fkn expression in glomerular endothelial cells (GECs) remains to be elucidated. Methods: We examined the effect of polyinosinic-polycytidylic acid (poly IC) on Fkn expression in cultured human GECs. Fkn mRNA and protein levels were quantified by real-time PCR and enzyme-linked immunosorbent assay, respectively. To further elucidate the effects of poly IC on this signaling pathway, we used small-interfering RNA (siRNA) to knockdown expression of TLR3, nuclear factor (NF)-kappa B p65, interferon (IFN)-beta, and IFN regulatory factor 3 (IRF3). We then analyzed whether pretreatment of chloroquine or dexamethasone (DEX) inhibits poly IC-induced Fkn expression. Results: We found that poly IC-induced Fkn expression in GECs, and that this involved NF-kappa B, IFN-beta, and IRF3. Pretreating cells with chloroquine, but not DEX attenuated poly IC-induced Fkn expression in GECs. Conclusion: Since the activation of TLR3/NF-kappa B/IFN-beta/Fkn and TLR3/IRF3/Fkn axes is involved in inflammatory reactions in GECs, intervention of glomerular TLR3 signaling may be a suitable therapeutic strategy for treating CGN especially LN.
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