title: Selective COX-2 inhibitor celecoxib prevents experimental autoimmune encephalomyelitis through COX-2-independent pathway.
abstract: Cyclooxygenase (COX) is a key enzyme of arachidonic acid metabolism and exists as two distinct isoforms. COX-1 is constitutively expressed in most tissues, whereas COX-2 is inducibly expressed at the site of inflammation. Selective inhibitors of COX-2 have been developed and have been used as anti-inflammatory agents. Here, we show that a new-generation COX-2 inhibitor, celecoxib, inhibited experimental autoimmune encephalomyelitis (EAE). Celecoxib, but not other COX-2 inhibitors such as nimesulid, prevented myelin oligodendrocyte glycoprotein (MOG) induced EAE when administrated orally on the day of disease induction. Moreover, celecoxib inhibited EAE in COX-2-deficient mice, indicating that celecoxib inhibited EAE in a COX-2-independent manner. In celecoxib-treated mice, interferon-gamma (IFN-gamma) production from MOG-specific T cells was reduced and MOG-specific IgG1 was elevated compared with vehicle-treated mice. Infiltration of inflammatory cells into the central nervous system and the expression of adhesion molecules, P-selectin and intercellular adhesion molecule-1 (ICAM-1), and a chemokine, monocyte chemoattractant peptide-1 (MCP-1), were inhibited when mice were treated with celecoxib. These results suggest that celecoxib may be useful as a new additional therapeutic agent for multiple sclerosis.
authors.affiliation: Department of Immunology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan.
authors.forename: Katsuichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyake
authors.forename: Miho
authors.initials: M
authors.lastname: Mizuno
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Oka
authors.forename: Susumu
authors.initials: S
authors.lastname: Kusunoki
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
mesh_terms: D000818:Animals; D000068579:Celecoxib; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D018932:Chemokine CCL2 / Q000097:blood; D051546:Cyclooxygenase 2 / Q000172:deficiency / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D017254:Leukemic Infiltration / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D011720:Pyrazoles / Q000627:therapeutic use*; D015398:Signal Transduction; D013449:Sulfonamides / Q000627:therapeutic use*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: C491768:Ccl2 protein, mouse; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D052246:Cyclooxygenase 2 Inhibitors; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib