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

The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
Youn Ju Lee, Jong Ryeol Eun

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 gava...Continue Reading

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Citations

Oct 30, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chi-Ren LiaoYueh-Hsiung Kuo
Apr 16, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Jung-Hye ShinDawon Kang
Aug 14, 2019·JGH Open : an Open Access Journal of Gastroenterology and Hepatology·Hiba A Al-KishaliHanan S El-Abhar
Jun 1, 2021·Immunopharmacology and Immunotoxicology·May Ahmed ShawkiRiham S Said

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Methods Mentioned

BETA
PCR
FACS
flow cytometry
ELISA

Software Mentioned

Cell Quest
Primer Express

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