Cross-talk between MEK1/2-ERK1/2 signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis rats

• Published in: Chinese medical journal Vol. 121; no. 22; pp. 2278 - 2283
• Main Authors: Zhang, Ling-ling, Wei, Wei, Wang, Qing-tong, Chen, Jing-yu, Chen, Yin
• Format: Journal Article
• Language: English
• Published: China Key Laboratory of Research & Development of Chinese Medicine in Anhui Province,Hefei,Anhui 230032,China 20.11.2008
• Subjects: Animals; Arthritis, Experimental - metabolism; Arthritis, Experimental - physiopathology; Blotting, Western; Butadienes - pharmacology; Cyclic AMP - metabolism; GTP-Binding Proteins - metabolism; Interleukin-1 - pharmacology; Isoproterenol - pharmacology; Male; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Nitriles - pharmacology; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Signal Transduction - physiology; Synovial Membrane - drug effects; Synovial Membrane - metabolism; Synovial Membrane - pathology; 关节炎; 胶原质; signaling; arthritis; cross-talk; MAP kinases; G protein
• ISSN: 0366-6999; 2542-5641
• DOI: 10.1097/00029330-200811020-00013

Background Signaling pathways that regulate the production of cytokines and destructive enzymes have been implicated in rheumatoid arthritis （RA） pathogenesis. There are co-relations between signaling pathways. The aim of this study was to investigate interactions and cross-talks between MEK1/2-extracellular signal-related kinase （ERK1/2） signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis （CIA） rats by the stimulation of interleukin-1 （IL-1）, U0126, isoprenaline hydrochloride and aminophyline respectively. Methods Twenty Sprague-Dawley （SD） rats were induced by chicken type II collagen. Synoviocytes of CIA rats were isolated and cultured. The expressions of Gi, phosphorylated MEK1/2 （p-MEK1/2） and phosphorylated ERK1/2 （p-ERK1/2） were detected by Western blotting, cAMP level and protein kinase A （PKA） activity were measured by radioimmunoassay and kinase-glo luminescent kinase assay respectively. Results There was remarkable inflammation in CIA rats accompanied by swelling paws, hyperplastic synovium, pannus and cartilage erosion, cAMP level and PKA activity of synoviocytes decreased. Gi, p-ERK1/2 and p-MEK1/2 increased, rlL-la improved the expression of Gi, p-ERK1/2 and p-MEK1/2, cAMP and PKA increased with stimulation of rlL-1α. U0126 inhibited Gi, cAMP and PKA of synoviocytes stimulated by rlL-la. Isoprenaline hydrochloride enhanced Gi, cAMP and PKA, but had no effects on p-MEK1/2 and p-ERK1/2. Aminophyline increased cAMP and PKA, but inhibited p-MEK1/2 and p-ERK1/2. Conclusions Mitogen-activated protein kinases （MAPKs） and G protein-couple signaling are associated with synovitis. There are cross talks between MAPKs and G protein-couple signaling. The two signaling pathways represent potential therapeutic targets for RA.