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

Ling Ling Zhang, Wei Wei, Qingtong Wang, Jing Yu Chen, Yin Chen

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 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. rIL-1α improved the expression of Gi, p-ERK1/2 and p-MEK1/2. cAMP and PKA increased with stimulation of rIL-1α. U0126 inhibited Gi, cAMP and PKA of synoviocytes stimulated by rIL-1α. 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.

Original languageEnglish (US)
Pages (from-to)2278-2283
Number of pages6
JournalChinese Medical Journal
Volume121
Issue number22
StatePublished - Nov 20 2008
Externally publishedYes

Keywords

  • Arthritis
  • Cross-talk
  • G protein
  • MAP kinases
  • Signaling

ASJC Scopus subject areas

  • Medicine(all)

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