title: Cilostazol Suppresses IL-23 Production in Human Dendritic Cells via an AMPK-Dependent Pathway.
abstract: OBJECTIVE
  Cilostazol has been previously demonstrated to inhibit IL-23 production in human synovial macrophages via a RhoA/ROCK-dependent pathway. However, whether cilostazol affects IL-23 production in human dendritic cells remains largely unknown. The present study was designed to investigate this question and elucidate the possible underlying mechanisms.
  
  
  METHODS
  Human monocyte-derived dendritic cells (mo-DCs) were pretreated with or without cilostazol and then incubated with zymosan. Enzyme-linked immunosorbent assay (ELISA) and real time PCR analyses were used to measure IL-23 protein expression and RNA levels, respectively, whereas Western blotting was used to measure the expression and phosphorylation level of AMPK.
  
  
  RESULTS
  Our results demonstrated that cilostazol suppressed zymosan-induced IL-23 protein production in a concentration dependent manner without affecting dendritic cell viability. In addition, it was found that cilostazol suppressed the expression of the p19 and p40 subunits of IL-23. Moreover, cilostazol mimicked the effect of the AMPK agonist A-769662, as demonstrated by the fact that IL-23 production was also inhibited by A-769662, and the effect of cilostazol on IL-23 production was blocked by the AMPK antagonist Compound C. More importantly, Western blotting demonstrated that cilostazol led to an increased phosphorylation of AMPK.
  
  
  CONCLUSIONS
  Collectively, our data suggest that cilostazol inhibits the production of IL-23 in human mo-DCs, potentially via the activation of AMPK. This suggests that cilostazol could be an effective anti-inflammatory agent in IL-23- and dendritic cell-related diseases.
authors.affiliation: Department of Cardiology, The 306th Hospital of Chinese PLA, Beijing, China.
authors.forename: Quanxing
authors.initials: Q
authors.lastname: Shi
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yin
authors.forename: Peilin
authors.initials: P
authors.lastname: Liu
authors.forename: Bei
authors.initials: B
authors.lastname: Zhao
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Shuai
authors.initials: S
authors.lastname: Mao
authors.forename: Tengfei
authors.initials: T
authors.lastname: Wei
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Rao
authors.forename: Liguo
authors.initials: L
authors.lastname: Zhang
authors.forename: Shouli
authors.initials: S
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D001713:Biphenyl Compounds; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D000077407:Cilostazol; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D053759:Interleukin-23 / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000166:cytology; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D021122:Protein Subunits / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D015054:Zymosan / Q000494:pharmacology
chemical_list: D001713:Biphenyl Compounds; D053759:Interleukin-23; D053594:Myeloid Differentiation Factor 88; D021122:Protein Subunits; D011753:Pyrones; D013777:Tetrazoles; D013876:Thiophenes; D015054:Zymosan; D055372:AMP-Activated Protein Kinases; D000077407:Cilostazol; C512408:4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile