Another important mechanism of the anti-inflammatory action of PPARα involves the catabolism of lipid mediators, such as leukotriene B
4 (LTB
4). The elegant study by Devchand and colleagues
[46] revealed that LTB
4 is a potent and specific PPARα ligand that induces expression of PPARα-transactivated genes of the peroxisomal β-oxidation pathway, namely, acyl-CoA oxidase, which is a rate-limiting enzyme of LTB
4 catabolism. PPARα
−/− mice subjected to a topical application of 5-LOX-inducing inflammatory agent and LTB
4 showed signs of tissue inflammation much longer (by about 30–40%) than wt mice, which were able to clear LTB
4 from circulation much faster
[46]. This experiment illustrates the importance of PPARα in the resolution of inflammation. This role of PPARα is necessary for regulation of the innate immune response, because proinflammatory lipid mediators, such as LTB
4, are not only strong chemotactic agents for neutrophils and other leukocytes, but they also facilitate PMNs extravasation and diapedesis at the local site of inflammation and increase vascular permeability in this region
[47][48]. By restricting LTB
4 duration, PPARα alleviates three out of four inflammation symptoms (heat, flushing, and edema). Moreover, PMNs are not only recipients of LTB
4 signals, but they are also activated to its production via a positive autocrine feedback loop
[49]. Therefore, the PPARα-regulated LTB
4 clearance protects from an overexaggerated inflammatory response and its transition from acute to destructive chronic state. The other eicosanoids, the products of either COX, i.e., prostaglandins PGD
1, PGD
2, PGA
1, and PGA
2, or 5-LOX product 8-(
S)-HETE, also activate PPARα
[50], which opens the possibility of modulating their impact on the cells with PPARα expression, whether in immunocompetent cells, such as monocytes/macrophages that express high levels of this receptor, or in the inflamed tissue. Such an activity contributes to tissue protection from inflammatory damage and facilitates regeneration.