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The anti‐spasticity drug baclofen alleviates collagen‐induced arthritis and regulates dendritic cells
Author(s) -
Huang Shichao,
Mao Jianxin,
Wei Bin,
Pei Gang
Publication year - 2015
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24884
Subject(s) - baclofen , spasticity , receptor , pharmacology , gabab receptor , immune system , medicine , dendritic cell , agonist , immunology , anesthesia
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. J. Cell. Physiol. 230: 1438–1447, 2015. © 2015 Wiley Periodicals, Inc., A Wiley Company