HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/2/G377    most recent 00147.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Tuin, A. Articles by Poelstra, K. Search for Related Content PubMed PubMed Citation Articles by Tuin, A. Articles by Poelstra, K.

INFLAMMATION/IMMUNITY/MEDIATORS

On the role and fate of LPS-dephosphorylating activity in the rat liver

Department of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Exploration, University of Groningen, Groningen, The Netherlands

Submitted 27 March 2005 ; accepted in final form 22 September 2005

Gut-derived lipopolysaccharide (LPS) plays a role in the pathogenesis of liver diseases like fibrosis. The enzyme alkaline phosphatase (AP) is present in, among others, the intestinal wall and liver and has been previously shown to dephosphorylate LPS. Therefore, we investigated the effect of LPS on hepatic AP expression and the effect of AP on LPS-induced hepatocyte responses. LPS-dephosphorylating activity was expressed at the hepatocyte canalicular membrane in normal and fibrotic animals. In addition to this, fibrotic animals also displayed high LPS-dephosphorylating activity around bile ducts. The enzyme was shown to dephosphorylate LPS from several bacterial species. LPS itself rapidly enhanced the intrahepatic mRNA levels for this enzyme within 2 h by a factor of seven. Furthermore, in vitro and in vivo studies showed that exogenous intestinal AP quickly bound to the asialoglycoprotein receptor on hepatocytes. This intestinal isoform significantly attenuated LPS-induced hepatic tumor necrosis factor- and nitric oxide (nitrite and nitrate) responses in vitro. The enzyme also reduced LPS-induced hepatic glycogenolysis in vivo. This study shows that LPS enhances AP expression in hepatocytes and that intestinal AP is rapidly taken up by these same cells, leading to an attenuation of LPS-induced responses in vivo. Gut-derived LPS-dephosphorylating activity or enzyme upregulation within hepatocytes by LPS may therefore be a protective mechanism within the liver.

lipopolysaccharide; inflammation; intestine; alkaline phosphatase

This article has been cited by other articles:

				T. Nakano, I. Inoue, D. H. Alpers, Y. Akiba, S. Katayama, R. Shinozaki, J. D. Kaunitz, S. Ohshima, M. Akita, S. Takahashi, et al. Role of lysophosphatidylcholine in brush-border intestinal alkaline phosphatase release and restoration Am J Physiol Gastrointest Liver Physiol, July 1, 2009; 297(1): G207 - G214. [Abstract] [Full Text] [PDF]