Celecoxib, a COX-2 inhibitor, synergistically potentiates the anti-inflammatory activity of docosahexaenoic acid in macrophage cell line.

Vijay Kumar Reddy, K. and Akhilender Naidu, K. (2016) Celecoxib, a COX-2 inhibitor, synergistically potentiates the anti-inflammatory activity of docosahexaenoic acid in macrophage cell line. Immunopharmacology and Immunotoxicology, 38 (2). pp. 153-161.

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Abstract

Background: The anti-inflammatory properties of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and non-steroidal anti-inflammatory drugs overlap in many ways. The aim of this study was to examine the individual and synergetic anti-inflammatory effects of celecoxib, EPA and DHA in RAW-264.7 cell line. Methodology: The cells were exposed to EPA, DHA, celecoxib, rosiglitazone, GW9662 alone or their combination, and stimulated with 5 mg/mL lipopolysaccharide (LPS). Nitric oxide (NO), tumor necrosis factor-a (TNF-a), interleukin (IL)-6 and prostaglandin-E2 (PGE2) levels were estimated in the medium using enzyme-linked immunosorbent assays. The cyclooxygenase-2 (COX-2) and inducible Nitric Oxide Synthase (iNOS) expression were analyzed in the cell lysate by immunoblotting. Peroxisome proliferator-activated receptor g (PPARg) and nuclear factor-kB (NF-kB) transcription factor activation assays were performed in the nuclear extract. Results: Combined treatment of DHA (50 mM) and celecoxib (20 mM) significantly inhibited LPS induced synthesis of NO, TNF-a, IL-6 and PGE2 levels in the cells, compared to the individual treatments. In addition, DHA and celecoxib diminished the COX-2 and iNOS expression in the cells. This was associated with increased PPARg activity, supressed NF-kB activity in the nucleus. We determined whether GW9662, a specific PPARg inhibitor, could abolish the antiinflammatory effect of DHA and celecoxib. GW9662 has abolished the DHA and celecoxib induced PPARg activation, but did not alter the NF-kB mediated anti-inflammatory effects induced by celecoxib and DHA. Interestingly, EPA did not exhibit any inhibitory effect on these parameters. Conclusion: Our results suggest that DHA and celecoxib exhibit anti-inflammatory effect through inhibition of NF-kB, independent of PPARg. Co-administration of celecoxib and DHA would be promising approach for the treatment of inflammatory diseases.

Item Type:	Article
Uncontrolled Keywords:	Celecoxib, DHA, EPA, inflammation, TNF-alpha
Subjects:	500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 11 Lipid Biochemistry
Divisions:	Dept. of Biochemistry
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	03 Jul 2017 11:14
Last Modified:	03 Jul 2017 11:14
URI:	http://ir.cftri.res.in/id/eprint/12743

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