The cyclooxygenase-2 pathway via the PGE₂ EP2 receptor contributes to oligodendrocytes apoptosis in cuprizone-induced demyelination.
作者： Sara Palumbo , Christopher D. Toscano , Laura Parente , Roberto Weigert , Francesca Bosetti
DOI: 10.1111/J.1471-4159.2011.07363.X
关键词: Myelin 、 Oligodendrocyte 、 Inflammation 、 Signal transduction 、 Receptor antagonist 、 Cyclooxygenase 、 Receptor 、 Biology 、 Immunology 、 Multiple sclerosis 、 Cancer research
摘要: Cyclooxygenases (COX)-1 and -2 are key enzymes required for the conversion of arachidonic acid to eicosanoids, potent mediators inflammation. In patients with multiple sclerosis, COX-2 derived prostaglandins (PGs) elevated in CSF is up-regulated demyelinating plaques. However, it not known whether activity contributes oligodendrocyte death. cuprizone-induced demyelination, apoptosis a concomitant increase gene expression PGE₂-EP2 receptor precede histological demyelination. EP2 were expressed by oligodendrocytes, suggesting causative role COX-2/EP2 pathway initiation death deletion, chronic treatment selective inhibitor celecoxib, or antagonist AH6809 reduced apoptosis, degree demyelination motor dysfunction. These data indicate that PGE₂ open possible new therapeutic approaches sclerosis.
sci-hub.se 参考文章(44)
Akhlaq A. Farooqui, Lloyd A. Horrocks, Tahira Farooqui, Modulation of inflammation in brain: a matter of fat. Journal of Neurochemistry. ,vol. 101, pp. 577- 599 ,(2006) , 10.1111/J.1471-4159.2006.04371.X
Y. Kihara, T. Matsushita, Y. Kita, S. Uematsu, S. Akira, J.-i. Kira, S. Ishii, T. Shimizu, Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis Proceedings of the National Academy of Sciences of the United States of America. ,vol. 106, pp. 21807- 21812 ,(2009) , 10.1073/PNAS.0906891106
K. Yoshikawa, S. Palumbo, C.D. Toscano, F. Bosetti, Inhibition of 5-lipoxygenase activity in mice during cuprizone-induced demyelination attenuates neuroinflammation, motor dysfunction and axonal damage Prostaglandins Leukotrienes and Essential Fatty Acids. ,vol. 85, pp. 43- 52 ,(2011) , 10.1016/J.PLEFA.2011.04.022
Anthony T. Reder, Manjula Thapar, Anna Maria Sapugay, Mark A. Jensen, Eicosenoids Modify Experimental Allergic Encephalomyelitis. American Journal of Therapeutics. ,vol. 2, pp. 711- 720 ,(1995) , 10.1097/00045391-199509000-00020
Chengcan Yao, Daiji Sakata, Yoshiyasu Esaki, Youxian Li, Toshiyuki Matsuoka, Kenji Kuroiwa, Yukihiko Sugimoto, Shuh Narumiya, Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nature Medicine. ,vol. 15, pp. 633- 640 ,(2009) , 10.1038/NM.1968
Jia Ni, Ying-Yi Shu, Yi-Na Zhu, Yun-Feng Fu, Wei Tang, Xiang-Gen Zhong, Hui Wang, Yi-Fu Yang, Jin Ren, Ming-Wei Wang, Jian-Ping Zuo, COX-2 inhibitors ameliorate experimental autoimmune encephalomyelitis through modulating IFN-γ and IL-10 production by inhibiting T-bet expression ☆ Journal of Neuroimmunology. ,vol. 186, pp. 94- 103 ,(2007) , 10.1016/J.JNEUROIM.2007.03.012
Michael H. Barnett, John W. Prineas, Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Annals of Neurology. ,vol. 55, pp. 458- 468 ,(2004) , 10.1002/ANA.20016
P. Dore-Duffy, S.-Y. Ho, C. Donovan, Cerebrospinal fluid eicosanoid levels: endogenous PGD2 and LTC4 synthesis by antigen-presenting cells that migrate to the central nervous system. Neurology. ,vol. 41, pp. 322- 322 ,(1991) , 10.1212/WNL.41.2_PART_1.322
Saba Aïd, Francesca Bosetti, Gene expression of cyclooxygenase-1 and Ca2+-independent phospholipase A2 is altered in rat hippocampus during normal aging Brain Research Bulletin. ,vol. 73, pp. 108- 113 ,(2007) , 10.1016/J.BRAINRESBULL.2007.02.015
Larry Schmued, William Slikker, Black-Gold: a simple, high-resolution histochemical label for normal and pathological myelin in brain tissue sections Brain Research. ,vol. 837, pp. 289- 297 ,(1999) , 10.1016/S0006-8993(99)01624-8