title: Secretory phospholipase A2 IIA is up-regulated by TNF-alpha and IL-1alpha/beta after transient focal cerebral ischemia in rat.
abstract: 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.
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, and Veterans Administration Hospital, Madison, WI 53705, USA. adibhatl@neurosurg.wisc.edu
authors.forename: Rao Muralikrishna
authors.initials: RM
authors.lastname: Adibhatla
authors.forename: J F
authors.initials: JF
authors.lastname: Hatcher
mesh_terms: 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*
chemical_list: 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