Secretory phospholipase A2 IIA is up-regulated by TNF-α and IL-1α/β after transient focal cerebral ischemia in rat

Cerebral ischemia initiates an inflammatory response in the brain that is associated with induction of a variety of cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1α/β (IL-1α/β) that contributes to stroke injury. Transient middle cerebral artery occlusion (tMCAO) in spontaneously hypertensive rat (SHR) resulted in significant increases in TNF-α and IL-1β levels. We have previously demonstrated up-regulation of secretory phospholipase A 2 IIA (sPLA 2 IIA) mRNA and protein expression, increased PLA 2 activity, and loss of phosphatidylcholine after 1 hr tMCAO and 24 hr reperfusion in SHR. Treatment with TNF-α antibody or IL-1 receptor antagonist significantly attenuated infarction volume, sPLA 2 IIA protein expression, PLA 2 activity and significantly restored phosphatidylcholine levels after tMCAO. This suggests that cytokine induction up-regulates sPLA 2 IIA protein expression, resulting in altered lipid metabolism that contributes to stroke injury.