Protective effect of cytosolic phospholipase A2 inhibition against inflammation and degeneration by promoting regulatory T cells in rats with experimental autoimmune encephalomyelitis.
Cytosolic phospholipase A2 (cPLA2) is the rate-limiting enzyme that initiates the production of various inflammatory mediators. Previous studies have shown that inhibiting cPLA2 exerts a neuroprotective effect on experimental autoimmune encephalomyelitis (EAE) by ameliorating the severity of the disease and influencing Th1 and Th17 responses. However, it remains unclear whether treatment with a cPLA2 inhibitor will influence the regulatory T cells (Tregs) that play a critical role in maintaining immune homeostasis and preventing autoimmune diseases. In this study, the cPLA2 inhibitor AX059 reduced the onset and progression of EAE in Lewis rats. In addition, this effect was accompanied by activation of Tregs and alterations in the expression of their various cytokines. The study therefore demonstrated that Tregs are involved in the immunomodulatory effect mediated by cPLA2 inhibition. These findings may have clinical application in the treatment of multiple sclerosis.
Department of Neurology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150086, China.
Dan
D
Yang
Department of Molecular Biology and Genetic Engineering, Cancer Institute of Heilongjiang Province, Harbin Medical University, Harbin 150081, China.
Hong-Fei
HF
Ji
Department of Neurology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150086, China.
Xue-Mei
XM
Zhang
Department of Neurology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150086, China.
Hui
H
Yue
Department of Neurology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150086, China.
Lin
L
Lin
Department of Molecular Biology and Genetic Engineering, Cancer Institute of Heilongjiang Province, Harbin Medical University, Harbin 150081, China.
Yu-Yan
YY
Ma
Department of Neurology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150086, China.
Xiang-nan
XN
Huang
Department of Neurology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150086, China.
Jin
J
Fu
Department of Neurology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150086, China.
Wei-Zhi
WZ
Wang
D000577:Amides / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006706:Homeostasis; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D064801:Phospholipase A2 Inhibitors / Q000494:pharmacology; D054467:Phospholipases A2 / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
C541509:AX 059; D000577:Amides; D016207:Cytokines; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2