|
목적 : Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), along with its receptor fibroblast
growth factor-inducible (Fn)14, is associated with various biological activities including
inflammation. However, its role in the pathogenesis of Graves’ orbitopathy (GO) is unknown.
In this study, we investigated the mechanism by which TWEAK regulates inflammatory signaling
in orbital fibroblasts from GO patients.
방법 : Orbital tissue were obtained from surgical waste during orbital decompression surgery in GO patient and cosmetic blepharoplasty from non-GO healthy controls. mRNA level of TWEAK and tumor necrosis factor-α (TNFA) were compared between GO and non-GO orbital tissue with quantitative PCR. Expression of pro-inflammatory cytokines were evaluated in recombinant TWEAK (rTWEAK) treated primary cultured orbital fibroblasts.
결과 : TWEAK and TNFA mRNA levels were upregulated in GO as compared to non-GO tissue samples. TWEAK, TNF receptor (TNFR)1, TNFR2, and TNFR superfamily member 12A mRNA, and TWEAK and Fn14 protein levels were increased by interleukin (IL)-1β and TNF-α treatment. Exogenous recombinant TWEAK increased the transcript and protein expression of the pro-inflammatory cytokines IL-6, IL-8, and MCP-1 to a greater extent in GO than in non-GO cells, while treatment with the anti-Fn14 antibody ITEM4 suppressed TWEAK-induced pro-inflammatory cytokine release and hyaluronan production.
결론 : These results demonstrate that TWEAK/Fn14 signaling contributes to GO pathogenesis.
Moreover, serum TWEAK level is a potential diagnostic biomarker for inflammatory
GO, and modulating TWEAK activity may be an effective therapeutic strategy for suppressing
inflammation and tissue remodeling in GO.
|