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) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal 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 Google Scholar Google Scholar Articles by Campbell, J. S. Articles by Fausto, N. Search for Related Content PubMed PubMed Citation Articles by Campbell, J. S. Articles by Fausto, N.

Proinflammatory Cytokine Production in Liver Regeneration Is Myd88-Dependent, but Independent of Cd14, Tlr2, and Tlr4¹

Jean S. Campbell^2,*, Kimberly J. Riehle^2,*,, John T. Brooling^*, Renay L. Bauer^*, Claudia Mitchell^* and Nelson Fausto^3,*

^* Department of Pathology and Department of Surgery, University of Washington, Seattle, WA 98195

TNF and IL-6 are considered to be important to the initiation or priming phase of liver regeneration. However, the signaling pathways that lead to the production of these cytokines after partial hepatectomy (PH) have not been identified. Enteric-derived LPS appears to be important to liver regeneration, possibly by stimulating proinflammatory cytokine production after surgery. To determine whether LPS signaling pathways are involved in the regulation of the proinflammatory cytokines TNF and IL-6 during the priming phase of liver regeneration, we performed PH on mice lacking the TLRs Tlr4 and Tlr2, the LPS coreceptor, Cd14, and Myd88, an adapter protein involved in most TLR and IL-1R pathways. In MyD88 knockout (KO) mice after PH, both liver Tnf mRNA and circulating IL-6 levels were severely depressed compared with heterozygous or wild-type mice. Activation of STAT-3 and three STAT-3 responsive genes, Socs3, Cd14, and serum amyloid A2 were also blocked. In contrast, Tlr4, Tlr2, and Cd14 KO mice showed no deficits in the production of IL-6. Surprisingly, none of these KO mice showed any delay in hepatocyte replication. These data indicate that the LPS receptor TLR4, as well as TLR2 and CD14, do not play roles in regulating cytokine production or DNA replication after PH. In contrast, MyD88-dependent pathways appear to be responsible for TNF, IL-6, and their downstream signaling pathways.

Related articles in The JI:

IN THIS ISSUE

The JI 2006 176: 2051-2052. [Full Text]  

This article has been cited by other articles:

				K. J. Riehle, J. S. Campbell, R. S. McMahan, M. M. Johnson, R. P. Beyer, T. K. Bammler, and N. Fausto Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3 J. Exp. Med., January 21, 2008; 205(1): 91 - 103. [Abstract] [Full Text] [PDF]

				C. L. Stoick-Cooper, R. T. Moon, and G. Weidinger Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine Genes & Dev., June 1, 2007; 21(11): 1292 - 1315. [Abstract] [Full Text] [PDF]

				C. L. Stoick-Cooper, G. Weidinger, K. J. Riehle, C. Hubbert, M. B. Major, N. Fausto, and R. T. Moon Distinct Wnt signaling pathways have opposing roles in appendage regeneration Development, February 1, 2007; 134(3): 479 - 489. [Abstract] [Full Text] [PDF]

				R. Dajani, S. Sanlioglu, Y. Zhang, Q. Li, M. M. Monick, E. Lazartigues, T. Eggleston, R. L. Davisson, G. W. Hunninghake, and J. F. Engelhardt Pleiotropic functions of TNF-{alpha} determine distinct IKKbeta-dependent hepatocellular fates in response to LPS Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G242 - G252. [Abstract] [Full Text] [PDF]

				Y. P. Turmelle, O. Shikapwashya, S. Tu, P. W. Hruz, Q. Yan, and D. A. Rudnick Rosiglitazone inhibits mouse liver regeneration FASEB J, December 1, 2006; 20(14): 2609 - 2611. [Abstract] [Full Text] [PDF]