The Gap-junction inhibitor Carbenoxolone suppresses the differentiation of Th17 cells through inhibition of IL-23 expression in antigen presenting cells

Abstract Carbenoxolone (CBX) is a widely used gap-junction inhibitor. We have previously shown that treatment with CBX significantly delayed the onset of experimental autoimmune encephalomyelitis (EAE). However, the mechanism by which CBX delays the onset of EAE remains to be elucidated. Here, we sh...

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Bibliographic Details
Published in:Journal of neuroimmunology 2011-12, Vol.240, p.58-64
Main Authors: Endong, Li, Shijie, Jin, Sonobe, Yoshifumi, Di, Ma, Hua, Li, Kawanokuchi, Jun, Mizuno, Tetsuya, Suzumura, Akio
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
Anti-Ulcer Agents - therapeutic use
Antigen-Presenting Cells - cytology
Antigen-Presenting Cells - drug effects
Antigen-Presenting Cells - immunology
Carbenoxolone
Carbenoxolone - pharmacology
Cell Differentiation - drug effects
Cell Differentiation - immunology
Down-Regulation - drug effects
Down-Regulation - genetics
Down-Regulation - immunology
Encephalomyelitis, Autoimmune, Experimental - drug therapy
Encephalomyelitis, Autoimmune, Experimental - immunology
Encephalomyelitis, Autoimmune, Experimental - pathology
Experimental autoimmune encephalomyelitis
Gap Junctions - drug effects
Gap Junctions - immunology
IL-17
IL-23 p19
Interleukin-23 - antagonists & inhibitors
Interleukin-23 - biosynthesis
Mice
Mice, Inbred C57BL
Neurology
Protein phosphatase 2A
Th17 Cells - cytology
Th17 Cells - drug effects
Th17 Cells - immunology
Up-Regulation - drug effects
Up-Regulation - genetics
Up-Regulation - immunology
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Summary:Abstract Carbenoxolone (CBX) is a widely used gap-junction inhibitor. We have previously shown that treatment with CBX significantly delayed the onset of experimental autoimmune encephalomyelitis (EAE). However, the mechanism by which CBX delays the onset of EAE remains to be elucidated. Here, we show that CBX specifically inhibits the production of IL-23 by dendritic cells (DCs) and microglia in vitro. CBX treatment significantly reduced the population of Th17 cells in EAE mice. Furthermore, CBX downregulated the expression of IL-23 p19 via increased production of protein phosphatase 2A (PP2A). Thus, CBX may be an effective therapeutic strategy against Th17-mediated autoimmune diseases, such as multiple sclerosis.
ISSN:0165-5728
1872-8421
DOI:10.1016/j.jneuroim.2011.09.012