AJP - GI Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol (July 8, 2004). doi:10.1152/ajpgi.00184.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/5/G1044    most recent
00184.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jaruga, B.
Right arrow Articles by Gao, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jaruga, B.
Right arrow Articles by Gao, B.
Submitted on April 23, 2004
Accepted on July 1, 2004

IFN-{gamma}/STAT1 Acts as A Pro-inflammatory Signal in T Cell-mediated Hepatitis via Induction of Multiple Chemokines and Adhesion Molecules: A Critical Role of IRF-1

Barbara Jaruga1, Feng Hong1, Won-Ho Kim1, and Bin Gao1*

1 Section on Liver Biology, Laboratory of Physiologic Studies, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA

* To whom correspondence should be addressed. E-mail: bgao{at}mail.nih.gov.

We have previously shown that IFN-{gamma}/STAT1 plays an essential role in Concanavalin A (Con A)-induced T cell hepatitis via activation of apoptotic signaling pathways. Here we demonstrate that IFN-{gamma}/STAT1 also plays a crucial role in leukocyte infiltration into the liver in T cell hepatitis. After injection of Con A, leukocytes were significantly infiltrated into the liver, which was suppressed in IFN-{gamma} -/- and STAT1 -/- mice. Disruption of the IFN regulatory factor-1 (IRF-1) gene, a downstream target of IFN-{gamma}/STAT1, abolished Con A-induced liver injury and suppressed leukocyte infiltration into the liver. Additionally, Con A injection induced expression of a wide variety of chemokines and adhesion molecules in the liver. Among them, expression of ICAM-1, VCAM-1, Mig, CCL-20, ENA-78, ITAC, and IP-10 was markedly attenuated in IFN-{gamma} -/-, STAT1 -/- , and IRF-1 -/- mice. In primary mouse hepatocytes, Kupffer cells, and endothelial cells, in vitro treatment with IFN-{gamma} activated STAT1, STAT3, and IRF-1, and induced expression of VCAM-1, ICAM-1, Mig, ENA-78, I-TAC, and IP-10 mRNA. Induction of these chemokines and adhesion molecules was markedly diminished in STAT1-/- and IRF-1-/- hepatic cells compared to wild-type hepatic cells. These findings suggest that in addition to induction of apoptosis previously well documented, IFN-{gamma} also stimulated hepatocytes, sinusoidal endothelial cells, and Kupffer cells partly via an STAT1/IRF-1-dependent mechanism to produce multiple chemokines and adhesive molecules responsible for promoting infiltration of leukocytes and ultimately resulting in hepatitis.




This article has been cited by other articles:


Home page
 Toxicol SciHome page
P. J. Shaw, A. C. Ditewig, J. F. Waring, M. J. Liguori, E. A. Blomme, P. E. Ganey, and R. A. Roth
Coexposure of Mice to Trovafloxacin and Lipopolysaccharide, a Model of Idiosyncratic Hepatotoxicity, Results in a Unique Gene Expression Profile and Interferon Gamma-Dependent Liver Injury
Toxicol. Sci., January 1, 2009; 107(1): 270 - 280.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
F. Gong, Y. Shen, C. Zhang, J. Xu, X. Wu, Z. Hua, and Q. Xu
Dregea volubilis Ameliorates Concanavalin A-Induced Liver Injury by Facilitating Apoptosis of Activated T Cells
Experimental Biology and Medicine, September 1, 2008; 233(9): 1124 - 1132.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
D. Voskas, Y. Babichev, L. S. Ling, J. Alami, Y. Shaked, R. S. Kerbel, B. Ciruna, and D. J. Dumont
An eosinophil immune response characterizes the inflammatory skin disease observed in Tie-2 transgenic mice
J. Leukoc. Biol., July 1, 2008; 84(1): 59 - 67.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
K. Kusaba, H. Kai, M. Koga, N. Takayama, A. Ikeda, H. Yasukawa, Y. Seki, K. Egashira, and T. Imaizumi
Inhibition of Intrinsic Interferon-{gamma} Function Prevents Neointima Formation After Balloon Injury
Hypertension, April 1, 2007; 49(4): 909 - 915.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. Numata, M. Kubo, H. Watanabe, K. Takagi, H. Mizuta, S. Okada, S. L. Kunkel, T. Ito, and A. Matsukawa
Overexpression of Suppressor of Cytokine Signaling-3 in T Cells Exacerbates Acetaminophen-Induced Hepatotoxicity
J. Immunol., March 15, 2007; 178(6): 3777 - 3785.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
C. M. Lappas, Y.-J. Day, M. A. Marshall, V. H. Engelhard, and J. Linden
Adenosine A2A receptor activation reduces hepatic ischemia reperfusion injury by inhibiting CD1d-dependent NKT cell activation
J. Exp. Med., November 27, 2006; 203(12): 2639 - 2648.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
H. Holschermann, T. H.W. Stadlbauer, A. H. Wagner, H. Fingerhuth, H. Muth, S. Rong, F. Guler, H. Tillmanns, and M. Hecker
STAT-1 and AP-1 decoy oligonucleotide therapy delays acute rejection and prolongs cardiac allograft survival
Cardiovasc Res, August 1, 2006; 71(3): 527 - 536.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
T. O. Yarovinsky, M. P. Mohning, M. A. Bradford, M. M. Monick, and G. W. Hunninghake
Increased Sensitivity to Staphylococcal Enterotoxin B following Adenoviral Infection
Infect. Immun., June 1, 2005; 73(6): 3375 - 3384.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.