Regulatory role of p53 in experimental autoimmune encephalomyelitis.
The role of p53, a pro-apoptotic protein, in experimental autoimmune encephalomyelitis (EAE) was investigated using p53-deficient C57BL/6J mice. p53-deficient mice immunised with myelin oligodendrocyte glycoprotein (MOG) exhibited a more severe clinical course of EAE with more severe inflammation in the central nervous system (CNS) compared to wild-type littermates. While T and B cell responses of p53-deficient mice to MOG were comparable to those of wild-type littermates, significantly higher production of IL-6, granulocyte macrophage colony-stimulating factor and IL-10 was observed in lymphocytes exposed to MOG from p53-deficient mice than those from wild-type littermates. Furthermore, a flow cytometric analysis of Annexin V staining showed that apoptosis of CNS-infiltrating cells was less in p53-deficient mice with EAE compared to wild-type littermates. These results suggest that p53 may be involved in the regulatory process of EAE through the control of cytokine production and/or the apoptotic elimination of inflammatory cells.
Okuda
Yoshinobu
Y
Neuroimmunology Laboratory, Department of Biochemistry, La Trobe University, Bundoora, Victoria 3083, Australia. yoshiok@bioserve.latrob.edu.au
Okuda
Misa
M
Bernard
Claude C A
CC
D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009569:Nitric Oxide / Q000502:physiology; D009573:Nitrites / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D016207:Cytokines; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009573:Nitrites; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide