Blockade of cytosolic phospholipase A sub(2) alpha prevents experimental autoimmune encephalomyelitis and diminishes development of Th1 and Th17 responses

• Published in: Journal of neuroimmunology 2008-11, Vol.204 (1-2), p.29-37
• Main Authors: Marusic, S, Thakker, P, Pelker, J W, Stedman, N L, Lee, K L, McKew, J C, Han, L, Xu, X, Wolf, S F, Borey, A J, Cui, J, Shen, MWH, Donahue, F, Hassan-Zahraee, M, Leach, M W, Shimizu, T, Clark, J D
• Format: Article
• Language: English
• ISSN: 0165-5728
• DOI: 10.1016/j.jneuroim.2008.08.012

Cytosolic phospholipase A sub(2) alpha (cPLA sub(2) alpha ) is the rate-limiting enzyme for release of arachidonic acid, which is converted primarily to prostaglandins via the cyclooxygenase (COX) 1/2 pathways, and leukotrienes via the 5-lipoxygenase (LO) pathway. We utilized inhibitors of cPLA sub(2) alpha , COX-1/2 and 5-LO to determine the potential roles of these enzymes in development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Blocking cPLA sub(2) alpha prevented EAE development and greatly reduced antigen-induced production of Th1-type cytokines and IL-17. Blocking COX-1/2 delayed onset and reduced severity of EAE, and reduced production of Th1-type cytokines, but not IL-17. Blocking 5-LO delayed onset and reduced cumulative severity of EAE, but did not reduce production of Th1-type cytokines or IL-17. Finally, blockade of cPLA sub(2) alpha from the onset of clinical EAE reduced duration of EAE relapses. Therefore, cPLA sub(2) alpha represents a potential therapeutic target for treatment of MS.