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.
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.
Ulivi
Valentina
V
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Cancedda
Ranieri
R
Cancedda
Fiorella Descalzi
FD
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D002356:Cartilage / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004008:Diclofenac / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation; D004790:Enzyme Induction; D004794:Enzyme Repression; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism* / Q000517:prevention & control; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D010671:Phenylurea Compounds / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000209:Acute-Phase Proteins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002087:Butyrates; C453899:GW 7647; D007093:Imidazoles; D000071068:Lipocalin-2; D054834:Lipocalins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D015513:Oncogene Proteins; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C071332:Lcn2 protein, mouse; D004008:Diclofenac; C401311:GW 7845; D014443:Tyrosine; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone; C093642:SB 203580; D015230:Prostaglandin D2