The gap-junction inhibitor carbenoxolone suppresses the differentiation of Th17 cells through inhibition of IL-23 expression in antigen presenting cells.
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.
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Li
L
Endong
Jin
J
Shijie
Yoshifumi
Y
Sonobe
Ma
M
Di
Li
L
Hua
Jun
J
Kawanokuchi
Tetsuya
T
Mizuno
Akio
A
Suzumura
D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002229:Carbenoxolone / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017629:Gap Junctions / Q000187:drug effects* / Q000276:immunology; D053759:Interleukin-23 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D000897:Anti-Ulcer Agents; D053759:Interleukin-23; D002229:Carbenoxolone