title: C-C chemokine receptor type 4 antagonist Compound 22 ameliorates experimental autoimmune encephalomyelitis.
abstract: Chemokines and chemokine receptors play important roles in the immune response. We previously reported the pathogenic role of C-C chemokine receptor type 4 (CCR4) in experimental autoimmune encephalomyelitis (EAE). Here, we examined whether CCR4 antagonism modulates the disease course of EAE. Wild-type and CCR4-knockout mice were induced EAE and were administered Compound 22, an antagonist of CCR4. Compound 22 significantly ameliorated the severity of EAE in wild-type mice, but not in the CCR4-knockout mice. Compound 22 inhibited Th1 and Th17 polarization of antigen-induced T-cell responses. Therefore, CCR4 antagonists might be potential therapeutic agents for multiple sclerosis.
authors: Division of Neurology, Department of Internal Medicine 3, National Defense Medical College, Tokorozawa, Japan; Department of Internal Medicine, Japan Self Defense Forces Hanshin Hospital, Kawanishi, Japan.
authors: Kota
authors: K
authors: Moriguchi
authors: Department of Neurology, Kinki University School of Medicine, Osaka-Sayama, Japan. Electronic address: miyamoto@med.kindai.ac.jp.
authors: Katsuichi
authors: K
authors: Miyamoto
authors: Department of Neurology, Kinki University School of Medicine, Osaka-Sayama, Japan.
authors: Noriko
authors: N
authors: Tanaka
authors: Department of Neurology, Kinki University School of Medicine, Osaka-Sayama, Japan.
authors: Rino
authors: R
authors: Ueno
authors: Division of Chemotherapy, Kinki University Faculty of Pharmacy, Higashi-Osaka, , Japan.
authors: Takashi
authors: T
authors: Nakayama
authors: Department of Microbiology, Kinki University School of Medicine, Osaka-Sayama, Japan.
authors: Osamu
authors: O
authors: Yoshie
authors: Department of Neurology, Kinki University School of Medicine, Osaka-Sayama, Japan.
authors: Susumu
authors: S
authors: Kusunoki
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005452:Fluoresceins / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000633:toxicity; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D054398:Receptors, CCR4 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: C108722:2-(3-hydroxy-4,5-diiodo-6H-6-oxoxanthen-9-yl)benzoic acid; C515355:Ccr4 protein, mouse; D016207:Cytokines; D005452:Fluoresceins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D054398:Receptors, CCR4; C445081:myelin oligodendrocyte glycoprotein (35-55)
keywords: Chemokine receptor; Experimental autoimmune encephalomyelitis