title: The anti-spasticity drug baclofen alleviates collagen-induced arthritis and regulates dendritic cells.
abstract: Baclofen is used clinically as a drug that treats spasticity, which is a syndrome characterized by excessive contraction of the muscles and hyperflexia in the central nervous system (CNS), by activating GABA(B) receptors (GABA(B)Rs). Baclofen was recently reported to desensitize chemokine receptors and to suppress inflammation through the activation of GABA(B)Rs. GABA(B)Rs are expressed in various immune cells, but the functions of these receptors in autoimmune diseases remain largely unknown. In this study, we investigated the effects of baclofen in murine collagen-induced arthritis (CIA). Oral administration of baclofen alleviated the clinical development of CIA, with a reduced number of IL-17-producing T helper 17 (T(H)17) cells. In addition, baclofen treatment suppressed dendritic cell (DC)-primed T(H)17 cell differentiation by reducing the production of IL-6 by DCs in vitro. Furthermore, the pharmacological and genetic blockade of GABA(B)Rs in DCs weakened the effects of baclofen, indicating that GABA(B)Rs are the molecular targets of baclofen on DCs. Thus, our findings revealed a potential role for baclofen in the treatment of CIA, as well as a previously unknown signaling pathway that regulates DC function.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, P. R. China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Huang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Mao
authors.forename: Bin
authors.initials: B
authors.lastname: Wei
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced*; D001418:Baclofen / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002454:Cell Differentiation; D002470:Cell Survival; D003094:Collagen / Q000633:toxicity*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D055785:Gene Knockdown Techniques; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009125:Muscle Relaxants, Central / Q000494:pharmacology / Q000627:therapeutic use; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000502:physiology
chemical_list: D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D015850:Interleukin-6; D009125:Muscle Relaxants, Central; D018080:Receptors, GABA-B; D003094:Collagen; D001418:Baclofen