title: Sphingosine-1-phosphate inhibits interleukin-1β-induced inflammation             in human articular chondrocytes.
abstract: Sphingosine-1-phosphate (S1P) is a pluripotent lipid mediator that transmits signals through a family of G-protein-coupled receptors (GPCRs) to control diverse biological processes including inflammation and wound-healing. In this study, a novel biological activity of S1P in articular chondrocytes was identified. Human primary chondrocytes were cultured in a monolayer. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were performed to detect genes and proteins involved in inflammation and cartilage degradation when human primary chondrocytes were stimulated by interleukin (IL)-1β. Matrix metalloproteinase (MMP)-2 and MMP-9 activity was evaluated by gelatin zymography. Glycosaminoglycan (GAG) degradation was evaluated using the dimethylene blue method. Prostaglandin E2 (PGE2) was measured by enzyme-linked immunosorbent assay (ELISA). By using the S1P1 receptor agonist and antagonist, we discovered the key role played by S1P1 in the S1P-dependent inhibition of IL-1β-induced inflammation in human chondrocytes. S1P dose-dependently inhibited IL-1β-induced NF-κB p65, cyclooxygenase (COX)-2, MMP-1, MMP-3, MMP-13 and MMP-14 mRNA expression in human chondrocytes and IL-1β-induced PGE2 synthesis and GAG degradation in human cartilage explants. W146, a known S1P1 receptor antagonist, inhibited the active form of NF-κB p65 and COX-2 expression induced by IL-1β. The anti-inflammatory action of the S1P1 receptor agonist SEW2871 was similar to that of S1P. This study demonstrates that S1P has anti-inflammatory effects on chondrocytes via the S1P1 receptor. Our data suggest that targeting S1P and S1P1 may be a potential therapy for arthritis.
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine,                     Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Moon
authors.forename: Jae-Kyo
authors.initials: JK
authors.lastname: Jeong
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Seol
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000473:pathology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004790:Enzyme Induction / Q000187:drug effects; D005109:Extracellular Matrix; D006801:Humans; D053583:Interleukin-1beta / Q000502:physiology*; D007719:Knee Joint / Q000473:pathology; D008246:Lysophospholipids / Q000494:pharmacology*; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D059748:Proteolysis; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; D051996:Transcription Factor RelA; C060506:sphingosine 1-phosphate; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D053505:Matrix Metalloproteinases, Secreted; D013110:Sphingosine