Background The peroxisome proliferator- activated receptor-gamma coactivator-1beta (PGC-1β) is a transcriptional coactivator which plays important roles in regulating multiple aspects of energy metabolism and cytokine signaling pathways. It was reported that enhanced expression of PGC-1β can attenuate inflammatory activation of macrophages. However, the specific role of PGC-1β in rheumatoid arthritis (RA) remains unclear.
Objectives To investigate the expression of PGC-1β and its role in the proinflammatory effect of RA fibrolast-like synoviocyte (FLS).
Methods Synovial tissue was obtained by needle biopsy from knees of 8 active RA patients and 6 osteoarthritis (OA) patients (as less inflamed control) and FLS was then cultured. PGC-1β expression of mRNA and protein was detected by quantitative real-time RT-PCR (qRT-PCR) and Western blot analysis respectively. PGC-1β was depleted by Lentiviral-PGC-1β-RNAi. In PGC-1β knockdown RA-FLS, the mRNA expression of proinflammatory cytokines and MMPs were analyzed by qRT-PCR, activation of the mitogen-activated protein kinases, ERK, JNK, and p38, as well as NF-κB were determined by Western blot analysis.
Results (1) PGC1β mRNA and protein expression in FLS from RA patients was significantly enhanced than that in OA controls (3.18±1.72 vs 1.17±0.74, p=0.019, and 0.82±0.30vs0.36±0.10, p=0.003, respectively). (2) Retrovirally mediated stable expression of the distinct shRNA led to more than 60% knockdown of endogenous PGC-1β in RA-FLS., The mRNA expression of proinflammatory cytokines, including TNF-α, IL-6, IL-8, IL-1β, and MMP-3, MMP-13 in the PGC-1β knockdown RA-FLS was decreased, which implied down-regulating PGC-1β alleviates the proinflammatory effect of RA-FLS. Western blot results showed decreased p-ERK, p-p38 and p-NF-κB, but not p-JNK in the PGC-1β knockdown RA-FLS, which implied down-regulating PGC-1β visibly suppressed the activity of ERK, p38 and NF-κB except JNK (Fig. 1).
Conclusions Our results indicated that PGC-1β may play an important role in the proinflammatory effect of RA-FLS through ERK, p38 and NF-κB pathway.
Acknowledgements Supported by Chinese National Natural Science Research Grant (grant no. 81373183 and 81001334), Specialized Research Fund for the Doctoral Program of Higher Education (grant no.20130171110075) and the Guangdong Natural Science Foundation (grant no.S2013010014396).
Disclosure of Interest : None declared
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