SPLA 2 enzymes have been implicated in physiological functions, host defence and inflammation. Sequence homology analysis led to the identification of 10 mammalian enzymatically active sPLA 2s (nine of which are expressed in humans) and two sPLA 2-like proteins devoid of catalytic activity. They are typically ∼14–19 kDa heavily disulphide bridged proteins found not only in mammals, but also in insects, snake venoms, plants, bacteria, fungi and viruses (Kini, 2003 Lambeau & Gelb, 2008 Nagiec et al, 2004 Soragni et al, 2001 Zadori et al, 2001). The sPLA 2 family members are strikingly diverse. Deletion of group IV cPLA 2α confirms its essential role in parturition and fertility (Bonventre et al, 1997 Kudo & Murakami, 2002 Uozumi et al, 1997) and its contributions to diverse inflammatory processes (Hegen et al, 2003, 2006). The best characterized member of the PLA 2 family is cytosolic group IV PLA 2α, which is constitutively expressed in most tissues. There are over 25 mammalian PLA 2 isoforms that have been grouped into three major classes, namely the calcium-dependent and -independent intracellular enzymes, and calcium-dependent secreted PLA 2 (sPLA 2) (Schaloske & Dennis, 2006 Valentin & Lambeau, 2000). Phospholipase A 2 (PLA 2) comprise a diverse family whose members share the capacity to hydrolyse the sn-2 position of membrane glycerophospholipids, releasing fatty acids and lysophospholipids. These observations identify a novel anti-inflammatory function for a PLA 2 and identify group V sPLA 2 as a potential biotherapeutic for treatment of immune-complex-mediated inflammation. Mechanistically, group V sPLA 2 counter-regulation includes promotion of immune complex clearance by regulating cysteinyl leukotriene synthesis. Contrary to expectation, we find that the group V sPLA 2 isoform plays a novel anti-inflammatory role that opposes the pro-inflammatory activity of group IIA sPLA 2. To further understand the roles of sPLA 2 in disease, we quantified the expression of these enzymes in the synovial fluid in rheumatoid arthritis and used gene-deleted mice to examine their contribution in a mouse model of autoimmune erosive inflammatory arthritis. The functions of the secretory PLA 2 enzymes (sPLA 2), numbering nine members in humans, are poorly understood, though they have been shown to participate in lipid mediator generation and the associated inflammation. Phospholipase A 2 (PLA 2) catalyses the release of arachidonic acid for generation of lipid mediators of inflammation and is crucial in diverse inflammatory processes.
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