Alpha7 nAChR Expression Is Correlated with Arthritis Development and Inhibited by Sinomenine in Adjuvant-Induced Arthritic Rats.

Chong Peng,Sha-Sha Bai,Jing Li,Yan-Jun Lv,Liang Liu,Ke-Er Huang,Yan Dong,Lang Yi,Hua Zhou,Pei-Xun Wang,Jia-Yan Liu,Qing-Ping Shi

doi:10.1155/2019/3759304

Abstract

Sinomenine (SIN) is the active ingredient of the Chinese herb Sinomenium acutum that has been used to treat rheumatoid arthritis (RA) for about 30 years in China. Marked expression of the alpha7 nicotinic acetylcholine receptor (α7nAChR) in the joint synovium of RA patients suggested a relationship between α7nAChR and RA. This study investigated the relationship between α7nAChR and RA development and the effects of SIN on α7nAChR expression in vivo and in vitro. Sprague-Dawley rats were injected with complete Freund's adjuvant to induce arthritis and then treated with SIN or methotrexate (MTX) from day 0 to day 30. Four clinical parameters—paw volume, arthritic index (AI), serum TNF-α concentration, and erythrocyte sedimentation rate (ESR)—were measured. Splenic lymphocytes were isolated for Bacille Calmette Guerin (BCG) stimulation. α7nAChR expression in tissues and cells was examined by RT-PCR, western blot, immunofluorescence, flow cytometry, and immunohistochemistry. Cell proliferation was evaluated by the CCK-8 assay. The relationship between α7nAChR expression and the four clinical parameters was analyzed by single-factor correlation analysis. Our results showed that the paw volume, AI, TNF-α concentration, and ESR in adjuvant-induced arthritic (AIA) rats were reduced by SIN or MTX treatment. SIN decreased α7nAChR expression in tissues and cells compared to the model group, while MTX had no significant effect on α7nAChR expression. Moreover, there was a positive relationship between α7nAChR expression and paw swelling, AI, and TNF-α concentration. Splenic lymphocyte activation was accompanied by increased α7nAChR expression, while SIN treatment inhibited cell activation and downregulated α7nAChR expression. α7nAChR expression showed a positive correlation with the progression of RA in AIA rats that may involve lymphocyte activation. Different from MTX, the inhibition of SIN on α7nAChR expression might contribute to its antiarthritic effect, suggesting that SIN could be an important supplement to the treatment strategy for RA.

Highlights

Rheumatoid arthritis (RA) is a systemic inflammatory disease that affects 0.5-1.0% of the world population
arthritic index (AI), and TNF-α concentration increased from day 12 to 30, peaked on day 18 or 24, and declined
We found an elevation of α7nAChR expression in tissues, peritoneal macrophages, and splenic lymphocytes of adjuvant-induced arthritic (AIA) rats, which was consistent with previous observations of α7nAChR expression in the synovium and fibroblast-like synoviocytes of RA patients [3, 4]

Summary

Introduction

Rheumatoid arthritis (RA) is a systemic inflammatory disease that affects 0.5-1.0% of the world population. The severity and progression of RA are affected by susceptibility genes, environmental damage, epigenetic modifications, and posttranslational modifications [1, 2]. Recent studies found marked expression of the alpha nicotinic acetylcholine receptor (α7nAChR) in the synovial membranes of RA patients and RA fibroblast-like synoviocytes [3, 4]. Α7nAChR is an important receptor in the cholinergic antiinflammatory pathway (CAP) [5]. It was reported that a lack of α7nAChR increased the severity of collagen-induced arthritis (CIA) in α7nAChR−/− mice [8]. Another study found that a lack of α7nAChR inhibited development of arthritis [9]. The role of α7nAChR in the progression of RA remains unclear

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Results

Conclusion