Cross-talk between MEK1/2-ERK1/2 signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis rats.
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 aminophylline 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. rIL-1alpha improved the expression of Gi, p-ERK1/2 and p-MEK1/2. cAMP and PKA increased with stimulation of rIL-1alpha. U0126 inhibited Gi, cAMP and PKA of synoviocytes stimulated by rIL-1alpha. Isoprenaline hydrochloride enhanced Gi, cAMP and PKA, but had no effects on p-MEK1/2 and p-ERK1/2. Aminophylline 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.
Zhang
Ling-ling
LL
Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, China.
Wei
Wei
W
Wang
Qing-tong
QT
Chen
Jing-yu
JY
Chen
Yin
Y
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000503:physiopathology; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D002070:Butadienes; D007375:Interleukin-1; D009570:Nitriles; C113580:U 0126; D000242:Cyclic AMP; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019204:GTP-Binding Proteins; D007545:Isoproterenol