| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 152, 1577-1589, Copyright © 1998 by American Society for Investigative Pathology
REGULAR ARTICLES |
Y Yamada and N Fausto
Department of Pathology, University of Washington School of Medicine, Seattle 98195-7705, USA.
Signaling by tumor necrosis factor type 1 receptor (TNFR-1) is required for the initiation of liver regeneration after partial hepatectomy. Using knockout mice that lack either TNFR-1 or TNFR-2, we determined whether signaling through TNF receptors is important for liver injury and hepatocyte proliferation induced by carbon tetrachloride (CCl4). Lack of TNFR-1 inhibited hepatocyte DNA synthesis after CCl4 injection. At 44 hours after the injection, replication of hepatocytes in TNFR-1 was 50% to 90% lower than in wild-type (WT) animals, depending on the dose injected. In WT animals, hepatocyte replication was essentially completed by 4 days after CCl4 injection, but replication at a low level persisted in TNFR-1 mice for at least 2 weeks. TNFR-1 knockout mice had little detectable NF-kappa B and STAT3 binding during the first 5 hours after CCl4, high plasma TNF, and reduced levels of plasma interleukin (IL)-6 and liver IL-6 mRNA. Injection of IL-6 30 minutes before CCl4 administration corrected the deficiency of hepatocyte replication at 44 hours and restored STAT3 binding to normal levels. In contrast, mice lacking TNFR-2 did not differ significantly from WT mice in NF-kappa B and STAT3 binding, IL-6 and TNF levels, or hepatocyte replication. Although AP-1 binding was induced in WT TNFR-1 and TNFR-2 knockout mice, binding in TNFR-2 knockouts was lower than in WT mice. C/EBP binding was much lower in TNFR-1 and TNFR-2 knockout mice than in WT mice. As assessed by morphological analysis and alanine aminotransferase levels, the acute injury caused by CCl4 appeared to be similar in the three groups of animals, but subsequent regeneration was impaired in mice lacking TNFR-1. We conclude that a TNFR-1 signaling pathway involving NF-kappa B, IL-6, and STAT3 is an important component of the hepatocyte mitogenic response induced by CCl4 injury in mouse liver.
This article has been cited by other articles:
 |
|
 |
|
  M. J. J. Ronis, A. Butura, S. Korourian, K. Shankar, P. Simpson, J. Badeaux, E. Albano, M. Ingelman-Sundberg, and T. M. Badger Cytokine and Chemokine Expression Associated with Steatohepatitis and Hepatocyte Proliferation in Rats Fed Ethanol via Total Enteral Nutrition Experimental Biology and Medicine, March 1, 2008; 233(3): 344 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hamada, A. Sato, T. Hirano, T. Yamamoto, G. Son, M. Onodera, I. Torii, T. Nishigami, M. Tanaka, A. Miyajima, et al. Oncostatin M Gene Therapy Attenuates Liver Damage Induced by Dimethylnitrosamine in Rats Am. J. Pathol., September 1, 2007; 171(3): 872 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C Henderson, K. J Pollock, J. Frew, A. C Mackinnon, R. A Flavell, R. J Davis, T. Sethi, and K. J Simpson Critical role of c-jun (NH2) terminal kinase in paracetamol- induced acute liver failure Gut, July 1, 2007; 56(7): 982 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Campbell, K. J. Riehle, J. T. Brooling, R. L. Bauer, C. Mitchell, and N. Fausto Proinflammatory Cytokine Production in Liver Regeneration Is Myd88-Dependent, but Independent of Cd14, Tlr2, and Tlr4 J. Immunol., February 15, 2006; 176(4): 2522 - 2528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S C Afford and D H Adams Following the TRAIL from hepatitis C virus and alcohol to fatty liver Gut, November 1, 2005; 54(11): 1518 - 1520. [Full Text] [PDF]
|
|
|
|
|
|
M. Kresse, M. Latta, G. Kunstle, H.-M. Riehle, N. van Rooijen, H. Hentze, G. Tiegs, M. Biburger, R. Lucas, and A. Wendel Kupffer Cell-Expressed Membrane-Bound TNF Mediates Melphalan Hepatotoxicity via Activation of Both TNF Receptors J. Immunol., September 15, 2005; 175(6): 4076 - 4083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yang, S. T. Magness, R. Bataller, R. A. Rippe, and D. A. Brenner NF-{kappa}B activation in Kupffer cells after partial hepatectomy Am J Physiol Gastrointest Liver Physiol, September 1, 2005; 289(3): G530 - G538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Sanz, J B Pucilowska, S Liu, C M Rodriguez-Ortigosa, P K Lund, D A Brenner, C R Fuller, J G Simmons, A Pardo, M-L Martinez-Chantar, et al. Expression of insulin-like growth factor I by activated hepatic stellate cells reduces fibrogenesis and enhances regeneration after liver injury Gut, January 1, 2005; 54(1): 134 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Chen, G. L Tipoe, E. C Liong, H. S. So, K.-M. Leung, W.-M. Tom, P. C. Fung, and A. A Nanji Green tea polyphenols prevent toxin-induced hepatotoxicity in mice by down-regulating inducible nitric oxide-derived prooxidants Am. J. Clinical Nutrition, September 1, 2004; 80(3): 742 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Markiewski, D. Mastellos, R. Tudoran, R. A. DeAngelis, C. W. Strey, S. Franchini, R. A. Wetsel, A. Erdei, and J. D. Lambris C3a and C3b Activation Products of the Third Component of Complement (C3) Are Critical for Normal Liver Recovery after Toxic Injury J. Immunol., July 15, 2004; 173(2): 747 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Chiu, C. R. Gardner, D. M. Dambach, J. A. Brittingham, S. K. Durham, J. D. Laskin, and D. L. Laskin Role of p55 tumor necrosis factor receptor 1 in acetaminophen-induced antioxidant defense Am J Physiol Gastrointest Liver Physiol, November 1, 2003; 285(5): G959 - G966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Ren, A. Carpenter, C. Hogaboam, and L. Colletti Mitogenic Properties of Endogenous and Pharmacological Doses of Macrophage Inflammatory Protein-2 after 70% Hepatectomy in the Mouse Am. J. Pathol., August 1, 2003; 163(2): 563 - 570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. M. Apte, P. B. Limaye, D. Desaiah, T. J. Bucci, A. Warbritton, and H. M. Mehendale Mechanisms of Increased Liver Tissue Repair and Survival in Diet-Restricted Rats Treated with Equitoxic Doses of Thioacetamide Toxicol. Sci., April 1, 2003; 72(2): 272 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. M. Apte, P. B. Limaye, S. K. Ramaiah, V. S. Vaidya, T. J. Bucci, A. Warbritton, and H. M. Mehendale Upregulated Promitogenic Signaling via Cytokines and Growth Factors: Potential Mechanism of Robust Liver Tissue Repair in Calorie-Restricted Rats upon Toxic Challenge Toxicol. Sci., October 1, 2002; 69(2): 448 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hasmall, G. Orphanides, N. James, W. Pennie, K. Hedley, A. Soames, I. Kimber, and R. Roberts Downregulation of Lactoferrin by PPAR{alpha} Ligands: Role in Perturbation of Hepatocyte Proliferation and Apoptosis Toxicol. Sci., August 1, 2002; 68(2): 304 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Anderson, C. S. Dunn, R. C. Cattley, and J.C. Corton Hepatocellular proliferation in response to a peroxisome proliferator does not require TNF{alpha} signaling Carcinogenesis, November 1, 2001; 22(11): 1843 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Wallenius, K. Wallenius, M. Hisaoka, J. Sandstedt, C. Ohlsson, M. Kopf, and J.-O. Jansson Retarded Liver Growth in Interleukin-6-Deficient and Tumor Necrosis Factor Receptor-1-Deficient Mice Endocrinology, July 1, 2001; 142(7): 2953 - 2960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Lawrence, G. K. Wollenberg, and J. G. DeLuca Tumor necrosis factor {{alpha}} is not required for WY14,643-induced cell proliferation Carcinogenesis, March 1, 2001; 22(3): 381 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wolf, R. Hallmann, G. Sass, M. Sixt, S. Kusters, B. Fregien, C. Trautwein, and G. Tiegs TNF-{{alpha}}-Induced Expression of Adhesion Molecules in the Liver Is Under the Control of TNFR1--Relevance for Concanavalin A-Induced Hepatitis J. Immunol., January 15, 2001; 166(2): 1300 - 1307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Knight, G. C.T. Yeoh, K. L. Husk, T. Ly, L. J. Abraham, C. Yu, J. A. Rhim, and N. Fausto Impaired Preneoplastic Changes and Liver Tumor Formation in Tumor Necrosis Factor Receptor Type 1 Knockout Mice J. Exp. Med., December 18, 2000; 192(12): 1809 - 1818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tomiya, I. Ogata, M. Yamaoka, M. Yanase, Y. Inoue, and K. Fujiwara The Mitogenic Activity of Hepatocyte Growth Factor on Rat Hepatocytes Is Dependent upon Endogenous Transforming Growth Factor-{alpha} Am. J. Pathol., November 1, 2000; 157(5): 1693 - 1701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. LUSTER, P. P. SIMEONOVA, R. M. GALLUCCI, A. BRUCCOLERI, M. E. BLAZKA, B. YUCESOY, and J. M. MATHESON The Role of Tumor Necrosis Factor {alpha} in Chemical-Induced Hepatotoxicity Ann. N.Y. Acad. Sci., September 1, 2000; 919(1): 214 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K L STREETZ, T LUEDDE, M P MANNS, and C TRAUTWEIN Interleukin 6 and liver regeneration Gut, August 1, 2000; 47(2): 309 - 312. [Full Text] [PDF]
|
|
|
|
|
|
R. H. Pierce, J. S. Campbell, A. B. Stephenson, C. C. Franklin, M. Chaisson, M. Poot, T. J. Kavanagh, P. S. Rabinovitch, and N. Fausto Disruption of Redox Homeostasis in Tumor Necrosis Factor-Induced Apoptosis in a Murine Hepatocyte Cell Line Am. J. Pathol., July 1, 2000; 157(1): 221 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Mahler The Use of Genetically Altered Animals in Toxicology Toxicol Pathol, May 1, 2000; 28(3): 447 - 449. [PDF]
|
|
|
|
|
|
C. M. Hogaboam, C. L. Bone-Larson, M. L. Steinhauser, A. Matsukawa, J. Gosling, L. Boring, I. F. Charo, K. J. Simpson, N. W. Lukacs, and S. L. Kunkel Exaggerated Hepatic Injury Due to Acetaminophen Challenge in Mice Lacking C-C Chemokine Receptor 2 Am. J. Pathol., April 1, 2000; 156(4): 1245 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Horn, T. D. O'Brien, L. B. Schook, and M. S. Rutherford Acute Hepatotoxicant Exposure Induces TNFR-Mediated Hepatic Injury and Cytokine/Apoptotic Gene Expression Toxicol. Sci., March 1, 2000; 54(1): 262 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Gallucci, P. P. Simeonova, W. Toriumi, and M. I. Luster TNF-{alpha} Regulates Transforming Growth Factor-{alpha} Expression in Regenerating Murine Liver and Isolated Hepatocytes J. Immunol., January 15, 2000; 164(2): 872 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Kirillova, M. Chaisson, and N. Fausto Tumor Necrosis Factor Induces DNA Replication in Hepatic Cells through Nuclear Factor {{kappa}}B Activation Cell Growth Differ., December 1, 1999; 10(12): 819 - 828. [Abstract] [Full Text]
|
|
|
|
|
|
N. Fausto Lessons From Genetically Engineered Animal Models. V. Knocking out genes to study liver regeneration: present and future Am J Physiol Gastrointest Liver Physiol, November 1, 1999; 277(5): G917 - G921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Roberts and I. Kimber Cytokines in non-genotoxic hepatocarcinogenesis Carcinogenesis, August 1, 1999; 20(8): 1397 - 1402. [Full Text] [PDF]
|
|
|
|
|
|
J. C.L. Schuh and K. A. Harrington Mechanisms of Disease and Injury: Utilization of Mutants, Monoclonals, and Molecular Methods Toxicol Pathol, January 1, 1999; 27(1): 115 - 120. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Prosch, A.-K. Heine, H.-D. Volk, and D. H. Kruger CCAAT/Enhancer-binding Proteins alpha and beta Negatively Influence the Capacity of Tumor Necrosis Factor alpha to Up-regulate the Human Cytomegalovirus IE1/2 Enhancer/Promoter by Nuclear Factor kappa B during Monocyte Differentiation J. Biol. Chem., October 26, 2001; 276(44): 40712 - 40720. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
