期刊
FASEB JOURNAL
卷 18, 期 3, 页码 489-498出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.03-0837com
关键词
resolution; cyclooxygenase; lipoxygenase; arachidonic acid; eicosanoids
Acute inflammation can be considered in terms of a series of checkpoints where each phase of cellular influx, persistence, and clearance is controlled by endogenous stop and go signals. It is becoming increasingly apparent that in addition to initiating the inflammatory response, eicosanoids may also mediate resolution. This suggests there are two phases of arachidonic acid release: one at onset for the generation of proinflammatory eicosanoids and one at resolution for the synthesis of proresolving eicosanoids. What is unclear is the identity of the phospholipase (PLA(2)) isoforms involved in this biphasic release of arachidonic acid. We show here that type VI iPLA(2) drives the onset of acute pleurisy through the synthesis of PGE(2), LTB4, PAF, and IL-1beta. However, during resolution there is a switch to a sequential induction of first sPLA(2) (types IIa and V) that mediates the release of PAY and lipoxin A, which, in turn, are responsible for the subsequent induction of type IV cPLA(2) that mediates the release of arachidonic acid for the synthesis of proresolving prostaglandins. This study is the first of its kind to address the respective roles of PLA(2) isoforms in acute resolving inflammation and to identify type VI iPLA(2) as a potentially selective target for the treatment of inflammatory diseases.
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