TY - JOUR
AU1 - Ayoub, Samir
AU2 - Botting, Regina
AU3 - Joshi, Amrish
AU4 - Seed, Michael
AU5 - Colville-Nash, Paul
AB - Cyclooxygenase-2 (COX-2) is an inducible isoform of the COX family of enzymes central to the synthesis of pro-inflammatory prostaglandins. Induction of COX-2 is mediated by many endogenous and exogenous molecules that include pro-inflammatory cytokines and bacterial lipopolysaccharide (LPS). It has been demonstrated that COX-2 can also be induced by diclofenac in cultured J774.2 macrophages. This induction was delayed compared to COX-2 induced by LPS and paracetamol selectively inhibited activity of this protein. The aim of the present study was to determine the transcription factor involved in the production of COX-2 after treatment of J774.2 cells with 500 μM diclofenac. Pre-treatment of cells with the peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonists GW9662 (0.1–1 μM) or biphenol A Diglycidyl Ether (100–200 μM) resulted in reduction of the induction of COX-2 by diclofenac, but not by LPS. Induction of COX-2 by the PPAR-γ agonist 15deoxyΔ12,14prostaglandin J2 was also reduced when the cells were pre-treated with the PPAR-γ antagonists BADGE or GW9662. On the other hand, pre-treatment of cells with the nuclear factor-kappa-B (NF-κB) Super-repressor IκBα (150–600 nM) reduced the induction of COX-2 by LPS, but not by diclofenac. We, therefore, have identified that PPAR-γ activation is a requirement for COX-2 induction after diclofenac stimulation of J774.2 cells. These results along with the finding that treatment of J774.2 macrophages with diclofenac resulted in the release of the anti-inflammatory cytokines, interleukin-10 and transforming growth factor-β suggest that the diclofenac-induced COX-2 protein may possess anti-inflammatory actions.
TI - Activation of macrophage peroxisome proliferator-activated receptor-γ by diclofenac results in the induction of cyclooxygenase-2 protein and the synthesis of anti-inflammatory cytokines
JF - Molecular and Cellular Biochemistry
DO - 10.1007/s11010-009-0048-y
DA - 2009-02-15
UR - https://www.deepdyve.com/lp/springer-journals/activation-of-macrophage-peroxisome-proliferator-activated-receptor-by-qfbn2FyIK2
SP - 101
EP - 110
VL - 327
IS - 2
DP - DeepDyve
ER -