15-deoxy-delta 12,14-prostaglandin J(2) inhibits the synthesis of the acute phase protein SIP24 in cartilage: Involvement of COX-2 in resolution of inflammation

J Cell Physiol. 2008 Nov;217(2):433-41. doi: 10.1002/jcp.21516.

Abstract

We previously demonstrated that, in the MC615 cartilage cell line, the p38/NF-kB pathway is activated both during differentiation and in response to an inflammatory stimulus. In both cases, the p38/NF-kB pathway activation leads to the expression of the lipocalin SIP24 and of COX-2. Given the fact that, in the same cells, the COX-2 expression is sustained during the inflammation resolution, at the same time that the SIP24 expression is suppressed, in the present study we tested the hypothesis that COX-2 products play a role in SIP24 repression. Taken together, our results suggest that, during the resolution of inflammation, COX-2 represses the acute phase protein SIP24 and restores physiological conditions, possibly through a pathway involving PPARgamma. Experimental evidences being the following: (1) 15-deoxy-delta 12,14-prostaglandin J(2), but not PGE(2): (i) inhibits the expression of SIP24 in the inflammatory phase and induces COX-2 synthesis; (ii) represses NF-kB activation induced by LPS; (iii) represses the synthesis of microsomal PGE Synthase-1 induced by LPS. (2) PPARgamma and PPARalpha are present in MC615 cells in both proliferating and hyperconfluent cultures. (3) PPARgamma ligand GW7845, but not PPARalpha ligand GW7647: (i) represses the expression of SIP24 induced by LPS; (ii) induces COX-2 expression. (4) p38 is involved in the PPARgamma mediated induction of COX-2. In fact 15-deoxy-delta 12,14-prostaglandin J(2) activates p38 and the cell pretreatment with the p38 specific inhibitor SB203580 represses the expression of COX-2 induced by both the 15-deoxy-delta12,14-prostaglandin J(2) and the PPARgamma ligand GW7845.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Butyrates / pharmacology
  • Cartilage / drug effects
  • Cartilage / enzymology*
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Chondrocytes / enzymology*
  • Cyclooxygenase 2 / biosynthesis*
  • Diclofenac / pharmacology
  • Dinoprostone / metabolism
  • Down-Regulation
  • Enzyme Induction
  • Enzyme Repression
  • Imidazoles / pharmacology
  • Inflammation / enzymology
  • Inflammation / metabolism*
  • Inflammation / prevention & control
  • Intramolecular Oxidoreductases / biosynthesis
  • Lipocalin-2
  • Lipocalins / metabolism*
  • Lipopolysaccharides / pharmacology
  • Mice
  • NF-kappa B / metabolism
  • Oncogene Proteins / metabolism*
  • Oxazoles / pharmacology
  • PPAR alpha / agonists
  • PPAR alpha / metabolism
  • PPAR gamma / agonists
  • PPAR gamma / metabolism
  • Phenylurea Compounds / pharmacology
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / metabolism
  • Prostaglandin-E Synthases
  • Protein Kinase Inhibitors / pharmacology
  • Pyridines / pharmacology
  • Signal Transduction
  • Time Factors
  • Tyrosine / analogs & derivatives
  • Tyrosine / pharmacology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Acute-Phase Proteins
  • Anti-Inflammatory Agents, Non-Steroidal
  • Butyrates
  • GW 7647
  • Imidazoles
  • Lipocalin-2
  • Lipocalins
  • Lipopolysaccharides
  • NF-kappa B
  • Oncogene Proteins
  • Oxazoles
  • PPAR alpha
  • PPAR gamma
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyridines
  • Lcn2 protein, mouse
  • Diclofenac
  • GW 7845
  • Tyrosine
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • p38 Mitogen-Activated Protein Kinases
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases
  • Ptges protein, mouse
  • Dinoprostone
  • SB 203580
  • Prostaglandin D2