New weapons against inflammation: dual inhibitors of phospholipase A2 and transglutaminase
J. Clin. Invest. Lucio Miele, et al. 111:19 doi:10.1172/JCI17506 [
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Figure 1sPLA
2s hydrolyze the ester bond at the
sn-2 position of membrane glycerophospholipids, generating free arachidonic acid. This acid is metabolized in a complex series of reactions involving COX or lipoxigenases (LOX), generating pro-inflammatory eicosanoids. TGase-catalyzed post-translational modifications activate sPLA
2, potentially increasing eicosanoid production during acute inflammation. The new recombinant peptides contain a pro-elafin sequence that inhibits TGase and an antiflammin sequence that inhibits sPLA
2. Thus they prevent TGase-induced sPLA
2 activation.
