V Wallenius1, K Wallenius, J O Jansson. 1. Research Center for Endocrinology and Metabolism, Dept. of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. ville.wallenius@medic.gu.se
Abstract
BACKGROUND/AIMS: In the absence of liver damage, rapid liver growth can be induced pharmacologically by so-called primary liver growth promoters. The importance of the acute-phase cytokines interleukin-6 and tumor necrosis factor-alpha for the actions of these compounds is not clear. This study aimed to investigate the importance of IL-6 and TNF-receptor-1 in pharmacologically-induced liver growth. METHODS: IL-6 knockout (IL-6(-/-)), TNF-receptor-1 knockout (TNFR1(-/-)) and wild-type mice were treated with the peroxisome proliferator nafenopin and the anti-androgen cyproterone acetate (CPA) in one single injection or for 6 days with daily injections, and examined at 24 or 48 h after treatment. In a control experiment, IL-6(-/-) mice were subjected to two-thirds partial hepatectomy. RESULTS: Nafenopin treatment increased relative liver weight and DNA synthesis similarly in IL-6(-/-), TNFR1(-/-) and wild-type mice. CPA increased liver weight similarly in all groups, but did not increase DNA synthesis. Expression of peroxisome proliferator activated receptor-alpha mRNA was increased in both IL-6(-/-) and wild-type mice by nafenopin treatment, but not by CPA treatment. After hepatectomy DNA synthesis was suppressed in IL-6(-/-) mice compared to wild-type mice. CONCLUSIONS: Liver growth induced by nafenopin and CPA was not dependent on the presence of IL-6 or TNF receptor-1, whereas liver regeneration was decreased in IL-6(-/-) mice.
BACKGROUND/AIMS: In the absence of liver damage, rapid liver growth can be induced pharmacologically by so-called primary liver growth promoters. The importance of the acute-phase cytokines interleukin-6 and tumor necrosis factor-alpha for the actions of these compounds is not clear. This study aimed to investigate the importance of IL-6 and TNF-receptor-1 in pharmacologically-induced liver growth. METHODS:IL-6 knockout (IL-6(-/-)), TNF-receptor-1 knockout (TNFR1(-/-)) and wild-type mice were treated with the peroxisome proliferator nafenopin and the anti-androgen cyproterone acetate (CPA) in one single injection or for 6 days with daily injections, and examined at 24 or 48 h after treatment. In a control experiment, IL-6(-/-) mice were subjected to two-thirds partial hepatectomy. RESULTS:Nafenopin treatment increased relative liver weight and DNA synthesis similarly in IL-6(-/-), TNFR1(-/-) and wild-type mice. CPA increased liver weight similarly in all groups, but did not increase DNA synthesis. Expression of peroxisome proliferator activated receptor-alpha mRNA was increased in both IL-6(-/-) and wild-type mice by nafenopin treatment, but not by CPA treatment. After hepatectomy DNA synthesis was suppressed in IL-6(-/-) mice compared to wild-type mice. CONCLUSIONS: Liver growth induced by nafenopin and CPA was not dependent on the presence of IL-6 or TNF receptor-1, whereas liver regeneration was decreased in IL-6(-/-) mice.
Authors: Guellue Cataldegirmen; Shan Zeng; Nikki Feirt; Nikalesh Ippagunta; Hao Dun; Wu Qu; Yan Lu; Ling Ling Rong; Marion A Hofmann; Thomas Kislinger; Sophia I Pachydaki; Daniel G Jenkins; Alan Weinberg; Jay Lefkowitch; Xavier Rogiers; Shi Fang Yan; Ann Marie Schmidt; Jean C Emond Journal: J Exp Med Date: 2005-02-07 Impact factor: 14.307