| Title | Cross-talk between MEK1/2-ERK1/2 signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis rats. | | Author(s) | Zhang LL, Wei W, Wang QT, Chen JY, Chen Y | | Institution | Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, China. | | Source | Chin Med J (Engl) 2008 Nov 20; 121(22):2278-83. | | MeSH | Animals
Arthritis, Experimental
Blotting, Western
Butadienes
Cyclic AMP
GTP-Binding Proteins
Interleukin-1
Isoproterenol
Male
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Nitriles
Radioimmunoassay
Rats
Rats, Sprague-Dawley
Signal Transduction
Synovial Membrane
| | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19080332 |
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