Secretory phospholipase A2 IIA is up-regulated by TNF-alpha and IL-1alpha/beta after transient focal cerebral ischemia in rat.
Cerebral ischemia initiates an inflammatory response in the brain that is associated with the induction of a variety of cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1alpha/beta (IL-1alpha/beta) that contributes to stroke injury. Transient middle cerebral artery occlusion (tMCAO) in spontaneously hypertensive rat (SHR) resulted in significant increases in TNF-alpha and IL-1beta levels. We have previously demonstrated up-regulation of secretory phospholipase A2 IIA (sPLA2 IIA) mRNA and protein expression, increased PLA2 activity, and loss of phosphatidylcholine after 1-h tMCAO and 24-h reperfusion in SHR. Treatment with TNF-alpha antibody or IL-1 receptor antagonist significantly attenuated infarction volume, sPLA2 IIA protein expression, PLA2 activity and significantly restored phosphatidylcholine levels after tMCAO. This suggests that cytokine induction up-regulates sPLA2 IIA protein expression, resulting in altered lipid metabolism that contributes to stroke injury.
Adibhatla
Rao Muralikrishna
RM
Department of Neurological Surgery, University of Wisconsin, and Veterans Administration Hospital, Madison, WI 53705, USA. adibhatl@neurosurg.wisc.edu
Hatcher
J F
JF
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002544:Cerebral Infarction / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004660:Encephalitis / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D054501:Group II Phospholipases A2; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D010713:Phosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D011918:Rats, Inbred SHR; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D000906:Antibodies; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2