Silybin inhibits interleukin-1β-induced production of pro-inflammatory mediators in canine hepatocyte cultures

A. Y. Au, J. M. Hasenwinkel, C. G. Frondoza

Research output: Contribution to journalArticle

Abstract

Hepatocytes are highly susceptible to cytokine stimulation and are fundamental to liver function. We established primary canine hepatocyte cultures to study effects of anti-inflammatory agents with hepatoprotective properties. Hepatocyte cultures were incubated with control media alone, silybin (SB), or the more bioavailable silybin-phosphatidylcholine complex (SPC), followed by activation with interleukin-1 beta (IL-1β; 10ng/mL). Inflammatory response was measured by prostaglandin E2 (PGE 2), interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) production and also nuclear factor-kappa B (NF-κB) translocation. Hepatocyte cultures continued production of the phenotypic marker albumin for more than 7days in culture. IL-1β exposure increased PGE 2, IL-8, and MCP-1 production, which was paralleled by NF-κB translocation from the cytoplasm to the nucleus. Pretreatment with SB and SPC significantly inhibited IL-1β-induced production of pro-inflammatory markers and attenuated NF-κB nuclear translocation. We demonstrate for the first time that primary canine hepatocyte cultures can be maintained in culture without phenotypic loss. The observation that hepatocyte cultures respond to pro-inflammatory IL-1β activation indicates hepatocytes as primary cellular targets of extrinsic IL-1β. The ability of SB and SPC to inhibit hepatocyte culture activation by IL-1β reinforces the notion of their hepatoprotective effects. Our primary canine hepatocyte culture model facilitates identification of hepatoprotective agents and their mechanism of action.

Original languageEnglish (US)
Pages (from-to)120-129
Number of pages10
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume34
Issue number2
DOIs
StatePublished - Apr 1 2011

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

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