S1P promotes IL-6 expression in osteoblasts through the PI3K, MEK/ERK and NF-κB signaling pathways

Int J Med Sci. 2020 May 18;17(9):1207-1214. doi: 10.7150/ijms.44612. eCollection 2020.

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks joint tissue. Interleukin (IL)-6 is a key proinflammatory cytokine in RA progression. Sphingosine-1-phosphate (S1P), a platelet-derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we examined the effects of S1P on IL-6 expression in osteoblasts. Our results and records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL-6 in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P increased mRNA and protein expression of IL-6. PI3K, MEK, ERK and NF-κB inhibitors and their small interfering RNAs (siRNAs) reduced S1P-promoted IL-6 expression. S1P also facilitated PI3K, MEK/ERK and NF-κB signaling cascades. Our results indicate that S1P promotes the expression of IL-6 in osteoblasts via the PI3K, MEK/ERK and NF-κB signaling pathways.

Keywords: Arthritis; IL-6; Osteoblasts; S1P.

MeSH terms

  • Blotting, Western
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interleukin-6 / metabolism*
  • Lysophospholipids / pharmacology*
  • NF-kappa B / metabolism*
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Synovial Fluid / metabolism

Substances

  • Interleukin-6
  • Lysophospholipids
  • NF-kappa B
  • sphingosine 1-phosphate
  • Sphingosine