Sinomenine inhibits fibroblast-like synoviocyte proliferation by regulating α7nAChR expression via ERK/Egr-1 pathway

Fibroblast like synoviocyte (FLS) is a crucial in the pathogenesis of rheumatoid arthritis (RA), and involved in inflammation and joint destruction. Sinomenine (SIN), an alkaloid derived from the plant Sinomenium acutum, has anti-inflammatory and analgesic effect and been used for RA treatment in China. Alpha 7 nicotinic acetylcholine receptors (alpha 7nAChR), as the key receptor in cholinergic anti-inflammatory pathway (CAP) to inhibit inflammation, has been detected in RA patients synovium, but its role is still unclear. Here we investigated the association between the aggressive proliferation of FLS and alpha 7nAChR expression and the effect of sinomenine. FLS was isolated from synovial tissues of adjuvant-induced-arthritis (AIA) rat. Tumor necrosis factor(TNF)-alpha was used to induce the aggressive proliferation of FLS. MIT assay was applied to evaluate the proliferation of FLS. The messenger RNA (mRNA) and protein levels of alpha 7nAChR and early growth response gene-1 (Egr-1) were measured. The results showed that INF-alpha induced FLS proliferation in vitro (P < .01) and increased the phosphorylation of ERK1/2 and the expression of Egr-1 and alpha 7nAChR (P < .05 or P < .01). U0126, the inhibitor of ERK1/2 inhibited alpha 7nAChR expression and FLS proliferation significantly (P < .05 or P < .01). Specific short interference RNA(siRNA) of alpha 7nAChR decreased alpha 7nAChR expression and inhibited FLS proliferation as well. SIN inhibited the proliferation of FLS and decreased the phosphorylation of ERK1/2, and the expression of Egr-1 and alpha 7nAChR induced by TNF-alpha (P < .05). In conclusion, the expression of alpha 7nAChR involved in the aggressive proliferation of FLS induced by INF-alpha and was regulated by ERK/Egr-1 signal pathway. SIN inhibited FLS proliferation and alpha 7nAChR expression through inhibiting ERK/Egr-1 signal pathway, this may contribute to the anti-inflammatory and anti-arthritic effect of SIN.