COX-2 in Inflammation and Resolution

Abstract

Aspirin and the other NSAIDs have popularized the notion of inhibiting prostaglandins as a common anti-inflammatory strategy based on the erroneous premise that all eicosanoids are, within the context of inflammation, generally detrimental. However, our fascination with aspirin and the emergence of COX-2 has shown a more affable side to lipid mediators based on our increasing interest in the endogenous control of acute inflammation and in factors that mediate its resolution. Epilipoxins, for instance, are produced from aspirin's acetylation of COX-2 and together with Resolvins and COX-2-derived prostaglandins of the D(2) and J(2) series represent an increasingly important family of immunoregulatory lipid mediators with strong implications for disease control and drug discovery.

Inflammatory pathways in female reproductive health and disease

“…Their release by phospholipases gives rise to arachidonic acid and lysophosphatidylcholine (Wymann & Schneiter 2008). Arachidonic acid is then enzymatically converted by cyclooxygenases (COX) to PG, prostacyclins and thromboxanes or by lipoxygenase (LOX) enzymes to leukotrienes (Rajakariar et al 2006, Wymann & Schneiter 2008. Lysophosphatidylcholine is in turn enzymatically converted to lysophosphatidic acid (LPA; Fig.…”

“…2; Mills & Moolenaar 2003, Wymann & Schneiter 2008. For many years the role of PGs in inflammation has been ascertained from studies conducted using nonsteroidal anti-inflammatory drugs (NSAIDs, which function by blocking COX-catalysed synthesis of prostanoids: PGs, prostacyclins and thromboxanes (Vane & Botting 1998); COX-enzyme-specific knock-out mice (Loftin et al 2002, Rajakariar et al 2006). At the onset of the inflammatory response, under the regulation of E 2 and progesterone (Critchley et al 2001), a range of growth factors, prostanoids, cytokines, chemokines and ILs promote the production of inflammatory prostanoids by inducing expression of COX enzymes.…”

γH2AX in Bystander Cells: Not Just a Radiation-Triggered Event, a Cellular Response to Stress Mediated by Intercellular Communication

“…Interestingly, catalase was recently demonstrated to be effective in abrogation of RIBE-induced DDR in human fibroblasts. 22 Moreover, cyclooxygenase-2 signaling, which is essential in mediating cellular inflammatory responses 37 was recently implicated as a crucial mediator of the bystander effect. 38,39 Therefore it is tempting to speculate that the release of reactive species including NO that occurs in inflammation is also a normal response of other cells to stress.…”

Resolvin D1 Improves the Resolution of Inflammation via Activating NF-κB p50/p50–Mediated Cyclooxygenase-2 Expression in Acute Respiratory Distress Syndrome

“…In addition to its well-known role as a pharmaceutical target for anti-inflammatory drugs in inflammatory diseases, COX-2 also exerts versatile biological activities to resolve inflammation (7)(8)(9). At the onset of inflammation, COX-2 has a potent proinflammatory effect, predominantly through the generation of PGE 2 , whereas in the resolution phase, COX-2 is responsible for producing proresolving PGs, such as PGD 2 , 15-deoxy-D 12,14 -PGJ 2 , and PGF 2a (10)(11)(12)(13).…”