title: Inhibition of sPLA₂-IIA prevents LPS-induced neuroinflammation by suppressing ERK1/2-cPLA₂α pathway in mice cerebral cortex.
abstract: Neuroinflammation is involved in various central nervous system (CNS) disorders, including brain infections, ischemia, trauma, stroke, and degenerative CNS diseases. In the CNS inflammation, secretory phospholipase A₂-IIA (sPLA₂-IIA) acts as a mediator, resulting in the generation of the precursors of pro-inflammatory lipid mediators, such as prostaglandins (PGs) and leukotrienes (LTs). However, the role of sPLA₂-IIA in neuroinflammation is more complicated and remains unclear yet. In the present study, we investigated the effect of sPLA₂-IIA inhibition by specific inhibitor SC-215 on the inflammation in LPS-induced mice cerebral cortex and primary astrocytes. Our results showed that the inhibition of sPLA₂-IIA alleviated the release of PGE₂ by suppressing the activation of ERK1/2, cPLA₂α, COX-2 and mPGES-1. These findings demonstrated that sPLA₂-IIA showed the potential to regulate the neuroinflammation in vivo and in vitro, indicating that sPLA₂-IIA might be a novel target for the treatment of acute neuroinflammation.
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Yanxiao
authors.initials: Y
authors.lastname: Xiang
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Liu
authors.forename: Xinbing
authors.initials: X
authors.lastname: Wei
authors.forename: Baozhu
authors.initials: B
authors.lastname: Sun
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000276:immunology; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D054501:Group II Phospholipases A2; D054510:Phospholipases A2, Cytosolic