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- Title
15-Deoxy-Δ[sup 12,14] -prostaglandin J[sub 2] inhibits IL-1β–induced cyclooxygenase-2 expression in mesangial cells.
- Authors
Sawano, Hirotaka; Haneda, Masakazu; Sugimoto, Toshiro; Inoki, Ken; Koya, Daisuke; Kikkawa, Ryuichi
- Abstract
Background. Cyclooxygenase-2 (COX-2), a key enzyme in the synthesis of prostaglandins, is induced in mesangial cells in response to proinflammatory cytokines. Recently, 15-deoxy-Δ[sup 12, 14]-prostaglandin J[sub 2] (15d-PGJ[sub 2]), one of the natural ligands of peroxisome proliferator-activated receptor γ (PPARγ), has been reported to have an anti-inflammatory effect. Therefore, we examined the effect of 15d-PGJ[sub 2] on COX-2 expression in cultured rat mesangial cells. Methods. Mesangial cells were incubated with 15d-PGJ[sub 2] for 30 minutes and then exposed to interleukin-lβ (IL-lβ). The expression of COX-2 mRNA and proteins was determined by Northern blot and immunoblot analyses, respectively. Accumulation of prostaglandin E[sub 2] (PGE[sub 2]) was measured by an enzyme-linked immunosorbent assay (ELISA). Activities of mitogen-activated protein kinases (MAPKs) were evaluated by an immunoblot analysis. DNA binding activities of activator protein-1 (AP-1) or nuclear factor-κB (NF-κB) were examined by an electrophoretic mobility shift assay (EMSA). The activities of PPAR responsive elements (PPRE) and COX-2 promoter were measured by a luciferase reporter assay. Results. 15D-PGJ[sub 2] significantly suppressed IL-lβ-induced COX-2 expression and PGE[sub 2] production, but thiazolidinediones, synthetic PPARγ ligands, did not affect COX-2 expression. Moreover, the cells transfected with a PPRE luciferase reporter did not respond to 15d-PGJ[sub 2]. IL-1β rapidly activated extracellular signal-regulated kinase (ERK) and c-Jun NH[sub 2]terminal kinase (JNK), which were involved in the up-regulation of COX-2 induction, but 15d-PGJ[sub 2] inhibited the activation of these kinases. 15d-PGJ[sub 2] inhibited the IL-lβ-induced increase in binding activities of nuclear proteins to consensus AP-1 site and AP-l-like site of COX-2 promoter but not of NF-κB. IL-β3 was unable to activate the COX-2 promoter...
- Subjects
KIDNEYS; CYCLOOXYGENASES; INTERLEUKIN-1; PROSTAGLANDINS; CYTOLOGY
- Publication
Kidney International, 2002, Vol 61, Issue 6, p1957
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2002.00351.x