Cilostazol decreases ethanol-mediated TNFalpha expression in RAW264.7 murine macrophage and in liver from binge drinking mice

Youn Ju Lee, Jong Ryeol Eun

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor α (TNFα) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNFα production in vitro and in vivo, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNFα mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP- activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNFα production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The in vivo effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNFα mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNFα production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNFα production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNFα production by cilostazol.

Original languageEnglish
Pages (from-to)131-138
Number of pages8
JournalKorean Journal of Physiology and Pharmacology
Volume16
Issue number2
DOIs
StatePublished - Apr 2012

Keywords

  • Alcoholic hepatitis
  • AMPK
  • Cilostazol
  • Macrophage
  • Tumor necrosis factor α

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