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

Autor: Au, A. Y., Hasenwinkel, J. M., Frondoza, C. G.
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Zdroj: Journal of Veterinary Pharmacology & Therapeutics; Apr2011, Vol. 34 Issue 2, p120-129, 10p, 2 Color Photographs, 1 Black and White Photograph, 3 Graphs
Abstrakt: Au, A. Y., Hasenwinkel, J. M., Frondoza, C. G. Silybin inhibits interleukin-1β-induced production of pro-inflammatory mediators in canine hepatocyte cultures. J. vet. Pharmacol. Therap., 120-129. 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; 10 ng/mL). Inflammatory response was measured by prostaglandin E2 (PGE), 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 7 days in culture. IL-1β exposure increased PGE, 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. [ABSTRACT FROM AUTHOR]
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