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Inhibition of sphingosine 1-phosphate (S1P) receptor 1/2/3 ameliorates biological dysfunction in rheumatoid arthritis fibroblast-like synoviocyte MH7A cells through Gαi/Gαs rebalancing
- Source :
- Clinical and experimental pharmacologyphysiologyREFERENCES. 48(8)
- Publication Year :
- 2020
-
Abstract
- Sphingosine 1-phosphate (S1P) exerts its various physiological and pathological effects by interacting with G protein-coupled receptors. In addition, S1P can induce biological dysfunction in fibroblast-like synoviocytes (FLSs) in the development of rheumatoid arthritis (RA). However, the mechanism underlying this S1P-induced dysfunction remains unclear. An imbalance between Gαi and Gαs can affect the level of cAMP, an important regulator of numerous cell functions. Therefore, we studied the effects of S1P receptor (S1PR) 1-, 2-, and 3-associated Gαi/Gαs imbalance on the biological function of rheumatoid arthritis fibroblast-like synoviocyte (MH7A cells). The results showed that blocking S1PR1/3 and Gαi, and activating Gαs, inhibited the proliferation, migration, invasion, and proinflammatory cytokine release of MH7A cells in a S1P-induced inflammation model, whereas suppressing S1PR2 only affected the invasion and the release of proinflammatory cytokines of these cells. Analysis of the expression of S1PR1/2/3 and Gαi/Gαs further showed that S1PR1/2/3 could regulate the Gαi/Gαs balance. Furthermore, our data suggested that the level of cAMP was also affected. Combined, our results showed that impaired S1PR1/2/3 signalling can affect MH7A cells biological function via Gαi/Gαs-cAMP signalling, which can provide a new idea for the treatment of RA.
- Subjects :
- 0301 basic medicine
Pharmacology
Fibroblast-like synoviocyte
Gs alpha subunit
Sphingosine
Physiology
Sphingosine-1-phosphate receptor
Synoviocytes
Proinflammatory cytokine
Cell biology
Arthritis, Rheumatoid
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
0302 clinical medicine
chemistry
030220 oncology & carcinogenesis
Physiology (medical)
Sphingosine-1-phosphate
Lysophospholipids
Sphingosine-1-Phosphate Receptors
S1PR1
S1PR2
Subjects
Details
- ISSN :
- 14401681
- Volume :
- 48
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Clinical and experimental pharmacologyphysiologyREFERENCES
- Accession number :
- edsair.doi.dedup.....4b998fe2e8fd14affb279161a205438e