NDLI: 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

Content Provider	Springer Nature Link
Author	Ayoub, Samir S. Botting, Regina M. Joshi, Amrish N. Seed, Michael P. Colville Nash, Paul R.
Copyright Year	2009
Abstract	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 15deoxyΔ$^{12,14}$prostaglandin J$_{2}$ 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.
Starting Page	101
Ending Page	110
Page Count	10
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	327
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2009-02-15
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cyclooxygenase-2 Diclofenac J774.2 Lipopolysaccharide Paracetamol Peroxisome proliferator-activated receptor-γ Cardiology Oncology Medical Biochemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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