Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6117305 | Immunology Letters | 2013 | 8 Pages |
Abstract
The role of PGD2 has been recognized in allergy, innate immunity and inflammation. Western blot analysis identified 21 kDa lipocalin (L)-prostaglandin D2 (PGD2) synthase (S) in human osteoarthritis (OA)-affected cartilage, whose expression was increased by IL-1β and TNFα. Similarly, PGD2 was spontaneously released by human OA-affected cartilage (and upregulated by IL-β) in ex vivo conditions and could be inhibited by indomethacin. Addition of PGD2 to human OA-affected cartilage significantly increased accumulation of PGE2, PGF1α, PGF2α, TXB2, but inhibited LTB4 and nitric oxide (NO) accumulation. Similarly, PGD2 (but not 13,14-dihydro-15-keto PGD2) augmented IL-1β induced PGE2 but inhibited IL-β induced nitric oxide (NO) in human chondrocytes. Celecoxib (10 μM) inhibits COX-1 mediated PGD2, and nitric oxide synthase (NOS) mediated NO in human OA-affected cartilage. Furthermore, celecoxib (1 μM) counter balances (IL-1β induced + PGD2 modulated) levels of NO and PGE2 in human OA-affected cartilage and chondrocytes to basal levels. These results show concentration-dependent, pro- and anti-inflammatory activity of PGD2 in human chondrocytes and cartilage, which can be neutralized by celecoxib. In view of the broad prostaglandin dependent and independent mechanism of action of celecoxib, these observations further reaffirm the broader role of celecoxib as a “Disease Modifying Drug” for human Osteoarthritis.
Keywords
arachidonate 5-lipoxygenaseProstaglandin F2 alphaPGJ2PGH2DP2ADAMTS-4H-PGDSPGF2α5-LOTXB2IL-1LTB4PGD2PPARγPGE2ADAMTs-5L-PGDSArachidonic acidthromboxane B2Celecoxibcyclooxygenase 1cyclooxygenase 2CartilageLeukotriene B4Nitric oxideHigh Mobility Group proteinProstaglandin D2Prostaglandin E2Prostaglandin H2ProstaglandinsPeroxisome proliferator-activated receptor gamma
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Authors
Mandar Dave, Ashok R. Amin,