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Cytosolic phospholipase A2 alpha-deficient mice are resistant to experimental autoimmune encephalomyelitis.
J Exp Med. 2005 Sep 19; 202(6):841-51.JE

Abstract

Experimental autoimmune encephalomyelitis (EAE), a Th1-mediated inflammatory disease of the central nervous system (CNS), is a model of human multiple sclerosis. Cytosolic phospholipase A2alpha (cPLA2alpha), which initiates production of prostaglandins, leukotrienes, and platelet-activating factor, is present in EAE lesions. Using myelin oligodendrocyte glycoprotein (MOG) immunization, as well as an adoptive transfer model, we showed that cPLA2alpha-/- mice are resistant to EAE. Histologic examination of the CNS from MOG-immunized mice revealed extensive inflammatory lesions in the cPLA2alpha+/- mice, whereas the lesions in cPLA2alpha-/- mice were reduced greatly or completely absent. MOG-specific T cells generated from WT mice induced less severe EAE in cPLA2alpha-/- mice compared with cPLA2alpha+/- mice, which indicates that cPLA2alpha plays a role in the effector phase of EAE. Additionally, MOG-specific T cells from cPLA2alpha-/- mice, transferred into WT mice, induced EAE with delayed onset and lower severity compared with EAE that was induced by control cells; this indicates that cPLA2alpha also plays a role in the induction phase of EAE. MOG-specific T cells from cPLA2alpha-/- mice were deficient in production of Th1-type cytokines. Consistent with this deficiency, in vivo administration of IL-12 rendered cPLA2alpha-/- mice susceptible to EAE. Our data indicate that cPLA2alpha plays an important role in EAE development and facilitates differentiation of T cells toward the Th1 phenotype.

Authors+Show Affiliations

Department of Inflammation, Wyeth Research, Cambridge, MA 02140, USA. smarusic@wyeth.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16172261

Citation

Marusic, Suzana, et al. "Cytosolic Phospholipase A2 Alpha-deficient Mice Are Resistant to Experimental Autoimmune Encephalomyelitis." The Journal of Experimental Medicine, vol. 202, no. 6, 2005, pp. 841-51.
Marusic S, Leach MW, Pelker JW, et al. Cytosolic phospholipase A2 alpha-deficient mice are resistant to experimental autoimmune encephalomyelitis. J Exp Med. 2005;202(6):841-51.
Marusic, S., Leach, M. W., Pelker, J. W., Azoitei, M. L., Uozumi, N., Cui, J., Shen, M. W., DeClercq, C. M., Miyashiro, J. S., Carito, B. A., Thakker, P., Simmons, D. L., Leonard, J. P., Shimizu, T., & Clark, J. D. (2005). Cytosolic phospholipase A2 alpha-deficient mice are resistant to experimental autoimmune encephalomyelitis. The Journal of Experimental Medicine, 202(6), 841-51.
Marusic S, et al. Cytosolic Phospholipase A2 Alpha-deficient Mice Are Resistant to Experimental Autoimmune Encephalomyelitis. J Exp Med. 2005 Sep 19;202(6):841-51. PubMed PMID: 16172261.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytosolic phospholipase A2 alpha-deficient mice are resistant to experimental autoimmune encephalomyelitis. AU - Marusic,Suzana, AU - Leach,Michael W, AU - Pelker,Jeffrey W, AU - Azoitei,Mihai L, AU - Uozumi,Naonori, AU - Cui,Junqing, AU - Shen,Marina W H, AU - DeClercq,Charlene M, AU - Miyashiro,Joy S, AU - Carito,Brenda A, AU - Thakker,Paresh, AU - Simmons,David L, AU - Leonard,John P, AU - Shimizu,Takao, AU - Clark,James D, PY - 2005/9/21/pubmed PY - 2005/11/16/medline PY - 2005/9/21/entrez SP - 841 EP - 51 JF - The Journal of experimental medicine JO - J Exp Med VL - 202 IS - 6 N2 - Experimental autoimmune encephalomyelitis (EAE), a Th1-mediated inflammatory disease of the central nervous system (CNS), is a model of human multiple sclerosis. Cytosolic phospholipase A2alpha (cPLA2alpha), which initiates production of prostaglandins, leukotrienes, and platelet-activating factor, is present in EAE lesions. Using myelin oligodendrocyte glycoprotein (MOG) immunization, as well as an adoptive transfer model, we showed that cPLA2alpha-/- mice are resistant to EAE. Histologic examination of the CNS from MOG-immunized mice revealed extensive inflammatory lesions in the cPLA2alpha+/- mice, whereas the lesions in cPLA2alpha-/- mice were reduced greatly or completely absent. MOG-specific T cells generated from WT mice induced less severe EAE in cPLA2alpha-/- mice compared with cPLA2alpha+/- mice, which indicates that cPLA2alpha plays a role in the effector phase of EAE. Additionally, MOG-specific T cells from cPLA2alpha-/- mice, transferred into WT mice, induced EAE with delayed onset and lower severity compared with EAE that was induced by control cells; this indicates that cPLA2alpha also plays a role in the induction phase of EAE. MOG-specific T cells from cPLA2alpha-/- mice were deficient in production of Th1-type cytokines. Consistent with this deficiency, in vivo administration of IL-12 rendered cPLA2alpha-/- mice susceptible to EAE. Our data indicate that cPLA2alpha plays an important role in EAE development and facilitates differentiation of T cells toward the Th1 phenotype. SN - 0022-1007 UR - https://www.unboundmedicine.com/medline/citation/16172261/Cytosolic_phospholipase_A2_alpha_deficient_mice_are_resistant_to_experimental_autoimmune_encephalomyelitis_ L2 - https://rupress.org/jem/article-lookup/doi/10.1084/jem.20050665 DB - PRIME DP - Unbound Medicine ER -