pid mediators such as LXs, resolvins, protectins, and maresins could be of benefit in lupus and other collagen vascular diseases. In this context, the role of PUFAs and their pro- and anti-inflammatory metabolites in inflammation appears to be important. Pro- and anti-inflammatory lipids and their role in lupus Inflammation is not a single event but a process in which cellular influx, persistence, and resolution of inflammation are controlled by several endogenous 
stop and go 2883-98-9 site signals. It is evident from the discussion that products from AA, EPA, and DHA not only form precursors to various proinflammatory molecules such as PGE2, PGF2, TXs, and LTs but also give rise to LXs and ATLs, resolvins, and protectins that are anti-inflammatory 154 Journal of Inflammation Research 2010:3 Dovepress Dovepress Current and emerging strategies for the treatment and management of SLe in nature. For these pro- and anti-inflammatory compounds to form, initial activation of PLA2 that releases the precursors from the cell membrane lipid pool is essential. Thus, there are two phases of release of PUFAs: one at onset of the generation of proinflammatory PGs, TXs, and LTs and one at the time PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19835934 of resolution for the synthesis of antiinflammatory LXs and ATLs, resolvins, and protectins. There are three classes of phospholipases that control the release of AA and other PUFAs: calcium-independent PLA 2, secretory PLA 2, and cytosolic PLA2.97 Each class of PLA2 is further divided into isoenzymes: 10 for mammalian sPLA2, at least three for cPLA2, and two for iPLA2. During the early phase of inflammation, COX-derived PGs and lipoxygenase-derived LTs initiate exudate formation and inflammatory cell influx.8 TNF- causes an immediate influx of neutrophils concomitant with PGE2 and LTB4 production, whereas during the phase of resolution of inflammation an increase in LXA4, PGD2, and its product 15deoxy1214PGJ2 formation occurs, which induces resolution of inflammation with a simultaneous decrease in PGE2 synthesis that stops neutrophil influx and enhances phagocytosis of debris.98,99 Thus, there appears to be two waves of release of AA and other PUFAs: one at the onset of inflammation that causes the synthesis and release of PGE2, and a second at resolution for the synthesis of anti-inflammatory PGD2, 15deoxy1214PGJ2, and LXs, which is necessary for the suppression of inflammation. Thus, COX-2 enzyme has both harmful and useful actions by virtue of its ability to give rise to proinflammatory and anti-inflammatory PGs and LXs. Increased type VI iPLA2 protein was found to be the principal isoform expressed from the onset of inflammation up to 24 h, whereas type IIa and V sPLA2 were expressed from the beginning of 48 h to 72 h. Type IV cPLA2 was not detectable during the early phase of acute inflammation but increased progressively during resolution, peaking at 72 h. This increase in type IV cPLA2 was mirrored by a parallel increase in COX-2 expression.100 The increase in cPLA2 and COX-2 occurred in parallel, suggesting a close enzymatic coupling between them. Thus, there is a clear-cut role for different types of PLA2 in distinct and different phases of inflammation. Selective inhibition of cPLA2 resulted in the reduction of proinflammatory molecules PGE2, LTB4, IL-1, and PAF. Furthermore, inhibition of types IIa and V sPLA2 not only decreased PAF and LXA4 but also resulted in a reduction in cPLA2 and COX-2 activities. These results suggest that sPLA2-derived PAF and LXA4 in