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S1P facilitates IL ‐1β production in osteoblasts via the JAK and STAT3 signaling pathways
Author(s) -
Hu SungLin,
Huang ChienChung,
Tseng TzuTing,
Liu ShanChi,
Tsai ChunHao,
Fong YiChin,
Tang ChihHsin
Publication year - 2020
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22935
Subject(s) - small interfering rna , osteoimmunology , stat3 , proinflammatory cytokine , signal transduction , microbiology and biotechnology , sphingosine , chemistry , cytokine , receptor , biology , immunology , inflammation , rna , rankl , biochemistry , gene , activator (genetics)
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks synovial joint tissues. Interleukin (IL)‐1β is a critical proinflammatory cytokine in RA progression. Sphingosine‐1‐phosphate (S1P), a platelet‐derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we investigated how S1P mediates IL‐1β expression in osteoblasts. Our analysis of records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL‐1β in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P concentration dependently increased mRNA and protein expression of IL‐1β. Elevations in IL‐1β mRNA expression induced by S1P were reduced by the small interfering RNA (siRNA) against the S1P 1 receptor. S1P also augmented JAK and STAT3 molecular cascades. We also found that JAK and STAT3 inhibitors and their siRNAs antagonized S1P‐promoted IL‐1β expression. Our results indicate that S1P promotes the expression of IL‐1β in osteoblasts via the S1P 1 receptor and the JAK and STAT3 signaling pathways.