| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892
T cell-mediated immune responses are implicated in the pathogenesis of a variety of liver disorders; however, the underlying mechanism remains obscure. Con A injection is a widely accepted mouse model to study T cell-mediated liver injury, in which STAT6 is rapidly activated. Disruption of the IL-4 and STAT6 gene by way of genetic knockout abolishes Con A-mediated liver injury without affecting IFN-
/STAT1, IL-6/STAT3, or TNF-
/NF-
B signaling or affecting NKT cell activation. Infiltration of neutrophils and eosinophils in Con A-induced hepatitis is markedly suppressed in IL-4 -/- and STAT6-/- mice compared with wild-type mice. IL-4 treatment induces expression of eotaxins in hepatocytes and sinusoidal endothelial cells isolated from wild-type mice but not from STAT6-/- mice. Con A injection induces expression of eotaxins in the liver and elevates serum levels of IL-5 and eotaxins; such induction is markedly attenuated in IL-4-/- and STAT6-/- mice. Finally, eotaxin blockade attenuates Con A-induced liver injury and leukocyte infiltration. Taken together, these findings suggest that IL-4/STAT6 plays a critical role in Con A-induced hepatitis, via enhancing expression of eotaxins in hepatocytes and sinusoidal endothelial cells, and induces IL-5 expression, thereby facilitating recruitment of eosinophils and neutrophils into the liver and resulting in hepatitis.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  B. Gao, S. Radaeva, and O. Park Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases J. Leukoc. Biol., September 1, 2009; 86(3): 513 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Miller, Y. Sun, and Y.-X. Fu Cutting Edge: B and T Lymphocyte Attenuator Signaling on NKT Cells Inhibits Cytokine Release and Tissue Injury in Early Immune Responses J. Immunol., July 1, 2009; 183(1): 32 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Jiang, R. Sun, R. Zhou, H. Wei, and Z. Tian TLR-9 Activation Aggravates Concanavalin A-Induced Hepatitis via Promoting Accumulation and Activation of Liver CD4+ NKT Cells J. Immunol., March 15, 2009; 182(6): 3768 - 3774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 M. N. Ajuebor, Z. Wondimu, C. M. Hogaboam, T. Le, A. E.I. Proudfoot, and M. G. Swain CCR5 Deficiency Drives Enhanced Natural Killer Cell Trafficking to and Activation within the Liver in Murine T Cell-Mediated Hepatitis Am. J. Pathol., June 1, 2007; 170(6): 1975 - 1988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zhu, S. Diem, L. M. Araujo, A. Aumeunier, J. Denizeau, E. Philadelphe, D. Damotte, M. Samson, P. Gourdy, M. Dy, et al. The Pro-Th1 Cytokine IL-12 Enhances IL-4 Production by Invariant NKT Cells: Relevance for T Cell-Mediated Hepatitis J. Immunol., May 1, 2007; 178(9): 5435 - 5442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Aoudjehane, P. Podevin, O. Scatton, P. Jaffray, I. Dusanter-Fourt, G. Feldmann, P.-P. Massault, L. Grira, A. Bringuier, B. Dousset, et al. Interleukin-4 induces human hepatocyte apoptosis through a Fas-independent pathway FASEB J, May 1, 2007; 21(7): 1433 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kawasuji, M. Hasegawa, M. Horikawa, T. Fujita, Y. Matsushita, T. Matsushita, M. Fujimoto, D. A. Steeber, T. F. Tedder, K. Takehara, et al. L-selectin and intercellular adhesion molecule-1 regulate the development of Concanavalin A-induced liver injury J. Leukoc. Biol., April 1, 2006; 79(4): 696 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Andrew, D. J. Newton, J. E. Dalton, C. E. Egan, S. J. Goodwin, D. Tramonti, P. Scott, and S. R. Carding Delineation of the Function of a Major {gamma}{delta} T Cell Subset during Infection J. Immunol., August 1, 2005; 175(3): 1741 - 1750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Sennello, R. Fayad, A. M. Morris, R. H. Eckel, E. Asilmaz, J. Montez, J. M. Friedman, C. A. Dinarello, and G. Fantuzzi Regulation of T Cell-Mediated Hepatic Inflammation by Adiponectin and Leptin Endocrinology, May 1, 2005; 146(5): 2157 - 2164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Jaruga, F. Hong, W.-H. Kim, and B. Gao IFN-{gamma}/STAT1 acts as a proinflammatory signal in T cell-mediated hepatitis via induction of multiple chemokines and adhesion molecules: a critical role of IRF-1 Am J Physiol Gastrointest Liver Physiol, November 1, 2004; 287(5): G1044 - G1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Jaruga, F. Hong, W.-H. Kim, R. Sun, S. Fan, and B. Gao Chronic alcohol consumption accelerates liver injury in T cell-mediated hepatitis: alcohol disregulation of NF-{kappa}B and STAT3 signaling pathways Am J Physiol Gastrointest Liver Physiol, August 1, 2004; 287(2): G471 - G479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Torpey, S. E. Maher, A. L. M. Bothwell, and J. S. Pober Interferon {alpha} but Not Interleukin 12 Activates STAT4 Signaling in Human Vascular Endothelial Cells J. Biol. Chem., June 18, 2004; 279(25): 26789 - 26796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sun, Z. Tian, S. Kulkarni, and B. Gao IL-6 Prevents T Cell-Mediated Hepatitis via Inhibition of NKT Cells in CD4+ T Cell- and STAT3-Dependent Manners J. Immunol., May 1, 2004; 172(9): 5648 - 5655. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
