Cilostazol Decreases Ethanol-Mediated TNFalpha Expression in RAW264.7 Murine Macrophage and in Liver from Binge Drinking Mice

Title
Cilostazol Decreases Ethanol-Mediated TNFalpha Expression in RAW264.7 Murine Macrophage and in Liver from Binge Drinking Mice
Author(s)
은종렬이윤주[이윤주]
Keywords
NECROSIS-FACTOR-ALPHA; KAPPA-B ACTIVATION; PROTEIN-KINASE ACTIVATION; OXYGEN SPECIES PRODUCTION; ALCOHOLIC HEPATITIS; KUPFFER CELLS; OXIDATIVE STRESS; REACTIVE OXYGEN; PHOSPHODIESTERASE INHIBITORS; INHALED LIPOPOLYSACCHARIDE
Issue Date
201204
Publisher
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
Citation
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY, v.16, no.2, pp.131 - 138
Abstract
Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor alpha (TNF alpha) 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 TNF alpha 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 TNF alpha 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 TNF alpha 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. TNF alpha 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 TNF alpha production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNF alpha production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNF alpha production by cilostazol.
URI
http://hdl.handle.net/YU.REPOSITORY/28672http://dx.doi.org/10.4196/kjpp.2012.16.2.131
ISSN
1226-4512
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의과대학 > 내과학교실 > Articles
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