Endothelial expression of fractalkine (CX3CL1) is induced by Toll-like receptor 3 signaling in cultured human glomerular endothelial cells.
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)-κB p65, interferon (IFN)-β, 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-κB, IFN-β, and IRF3. Pretreating cells with chloroquine, but not DEX attenuated poly IC-induced Fkn expression in GECs.Conclusion: Since the activation of TLR3/NF-κB/IFN-β/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.
['Hirono|Koji|K|', 'Imaizumi|Tadaatsu|T|', 'Aizawa|Tomomi|T|', 'Watanabe|Shojiro|S|', 'Tsugawa|Koji|K|', 'Shiratori|Toshihiro|T|', 'Kawaguchi|Shogo|S|', 'Seya|Kazuhiko|K|', 'Matsumiya|Tomoh|T|', 'Ito|Etsuro|E|', 'Tanaka|Hiroshi|H|']
D002478:Cells, Cultured D054428:Chemokine CX3CL1 D002738:Chloroquine D042783:Endothelial Cells D006801:Humans D016899:Interferon-beta D007678:Kidney Glomerulus D016328:NF-kappa B D011070:Poly I-C D015398:Signal Transduction D051196:Toll-Like Receptor 3
fractalkine (CX3CL1) Toll-like receptor 3 glomerular endothelial cells lupus nephritis Chloroquine