15-deoxy-delta 12,14-prostaglandin J2 inhibits the synthesis of the acute phase protein SIP24 in cartilage: Involvement of COX-2 in resolution of inflammation

• Published in: Journal of cellular physiology Vol. 217; no. 2; pp. 433 - 441
• Main Authors: Ulivi, Valentina, Cancedda, Ranieri, Cancedda, Fiorella Descalzi
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2008
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.21516

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 PPARγ. Experimental evidences being the following: (1) 15‐deoxy‐delta 12,14‐prostaglandin J2, but not PGE2: (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) PPARγ and PPARα are present in MC615 cells in both proliferating and hyperconfluent cultures. (3) PPARγ ligand GW7845, but not PPARα ligand GW7647: (i) represses the expression of SIP24 induced by LPS; (ii) induces COX‐2 expression. (4) p38 is involved in the PPARγ mediated induction of COX‐2. In fact 15‐deoxy‐delta 12,14‐prostaglandin J2 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 J2 and the PPARγ ligand GW7845. J. Cell. Physiol. 217: 433–441, 2008. © 2008 Wiley‐Liss, Inc.