Saturday November 21 2009 | Biotechnology feed | All feeds
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Saturday November 21 2009 | Biotechnology feed | All feeds
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PLA2, an unexploited target for inflammation and infectious diseases Phospholipase A2 (PLA2), the enzyme that cleaves phospholipids to produce lysophospholipids and free fatty acids, was originally identified as an intracellular protein involved in cell signaling and the production of free fatty acids such as arachidonic acid. Over the past decade however a family of secreted PLA2 enzymes has been characterized. It is now known that this family is comprised of at least 10 members with distinct cellular distribution and growing therapeutic potential. In particular sPLA2-V and sPLA2-X are selectively expressed in human airway epithelium and in the case of sPLA2-X, in various immune cells. The basal expression of a third enzyme, sPLA2-IIA is low but becomes highly expressed during inflammation and sepsis as a result of LPS, cytokine and NF-kappa B induction. This enzyme has become associated with allergic rhinitis, rheumatoid arthritis, septic shock and ARDS. The anti-inflammatory activity of glucocorticoid appears to be due in part to the down-regulation of PLA2-IIA expression, and together this body of evidence suggests that inhibition of PLA2-IIA represents a target for the treatment of inflammatory disease. On the other hand this enzyme has also been shown to possess bactericidal activity and hence molecules able to induce its expression may be of use in the treatment of infectious diseases. Finally, the selective expression of sPLA2-V and sPLA2-X suggests that these enzymes should be evaluated as targets for airway dysfunction. The PLA2 family thus represents a therapeutic target with ever-increasing potential. This potential is still to be realized with only a handful of enzyme inhibitors reported as being in pharmaceutical development. Link to journal abstract:
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