Hepatocellular proliferation in response to agonists of peroxisome proliferator-activated receptor alpha:a role for kupffer cells?

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Hepatocellular proliferation in response to agonists of peroxisome proliferator-activated receptor alpha:a role for kupffer cells?

Please use this identifier to cite or link to this item: http://dx.doi.org/10.1186/1477-3163-5-26

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dc.contributor.author Alsarra, Ibrahim A
dc.contributor.author Brockmann, William G
dc.contributor.author Cunningham, Michael L
dc.contributor.author Badr, Mostafa Z., 1950-
dc.date.accessioned 2012-08-29T15:28:02Z
dc.date.available 2012-08-29T15:28:02Z
dc.date.issued 2006-11-27
dc.identifier.citation Journal of Carcinogenesis. 2006 Nov 27;5(1):26
dc.identifier.uri http://dx.doi.org/10.1186/1477-3163-5-26
dc.identifier.uri http://hdl.handle.net/10355/15047
dc.description.abstract Abstract Background It has been proposed that PPARα agonists stimulate Kupffer cells in rodents which in turn, release mitogenic factors leading to hepatic hyperplasia, and eventually cancer. However, Kupffer cells do not express PPARα receptors, and PPARα agonists stimulate hepatocellular proliferation in both TNFα- and TNFα receptor-null mice, casting doubt on the involvement of Kupffer cells in the mitogenic response to PPARα agonists. This study was therefore designed to investigate whether the PPARα agonist PFOA and the Kupffer cell inhibitor methylpalmitate produce opposing effects on hepatocellular proliferation and Kupffer cell activity in vivo, in a manner that would implicate these cells in the mitogenic effects of PPARα agonists. Methods Male Sprague-Dawley rats were treated intravenously via the tail vein with methylpalmitate 24 hrs prior to perfluorooctanoic acid (PFOA), and were sacrificed 24 hrs later, one hr after an intraperitoneal injection of bromodeoxyuridine (BrdU). Sera were analyzed for TNFα and IL-1β. Liver sections were stained immunohistochemically and quantified for BrdU incorporated into DNA. Results Data show that PFOA remarkably stimulated hepatocellular proliferation in the absence of significant changes in the serum levels of either TNFα or IL-1β. In addition, methylpalmitate did not alter the levels of these mitogens in PFOA-treated animals, despite the fact that it significantly blocked the hepatocellular proliferative effect of PFOA. Correlation between hepatocellular proliferation and serum levels of TNFα or IL-1β was extremely poor. Conclusion It is unlikely that mechanisms involving Kupffer cells play an eminent role in the hepatic hyperplasia, and consequently hepatocarcinogenicity attributed to PPARα agonists. This conclusion is based on the above mentioned published data and the current findings showing animals treated with PFOA alone or in combination with methylpalmitate to have similar levels of serum TNFα and IL-1β, which are reliable indicators of Kupffer cell activity, despite a remarkable difference in hepatocellular proliferation.
dc.title Hepatocellular proliferation in response to agonists of peroxisome proliferator-activated receptor alpha:a role for kupffer cells?
dc.type Journal Article
dc.date.updated 2012-08-29T15:28:03Z
dc.description.version Peer Reviewed
dc.language.rfc3066 en
dc.rights.holder Ibrahim A Alsarra et al.; licensee BioMed Central Ltd.


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