TNF-α-induced expression of adhesion molecules in the liver is under the control of TNFR1--relevance for concanavalin A-induced hepatitis

D. Wolf, R. Hallmann, G. Sass, M.K. Sixt, S. Küsters, B. Fregien, C. Trautwein, G. Tiegs, Journal of Immunology 166 (2001) 1300–1307.

Download
No fulltext has been uploaded. References only!
Journal Article | Published
Author
; ; ; ; ; ; ;
Abstract
TNF-alpha has been clearly identified as central mediator of T cell activation-induced acute hepatic injury in mice, e.g., Con A hepatitis. In this model, liver injury depends on both TNFRs, i.e., the 55-kDa TNFR1 as well as the 75-kDa TNFR2. We show in this report that the hepatic TNFRs are not transcriptionally regulated, but are regulated by receptor shedding. TNF directly mediates hepatocellular death by activation of TNFR1 but also induces the expression of inflammatory proteins, such as cytokines and adhesion molecules. Here we provide evidence that resistance of TNFR1(-/-) and TNFR2(-/-) mice against Con A hepatitis is not due to an impaired production of the central mediators TNF and IFN-gamma. Con A injection results in a massive induction of ICAM-1, VCAM-1, and E-selectin in the liver. Lack of either one of both TNFRs did not change adhesion molecule expression in the livers of Con A-treated mice, presumably reflecting the fact that other endothelial cell-activating cytokines up-regulated adhesion molecule expression. However, treatment of TNFR1(-/-) and TNFR2(-/-) mice with murine rTNF revealed a predominant role for TNFR1 for the induction of hepatic adhesion molecule expression. Pretreatment with blocking Abs against E- and P-selectin or of ICAM(-/-) mice with anti-VCAM-1 Abs failed to prevent Con A hepatitis, although accumulation of the critical cell population, i.e., CD4(+) T cells was significantly inhibited. Hence, up-regulation of adhesion molecules during acute hepatitis unlikely contributes to organ injury but rather represents a defense mechanism.
Publishing Year
Date Published
2001-01-15
Journal Title
Journal of Immunology
Volume
166
Issue
2
Page
1300 - 1307
IST-REx-ID

Cite this

Wolf D, Hallmann R, Sass G, et al. TNF-α-induced expression of adhesion molecules in the liver is under the control of TNFR1--relevance for concanavalin A-induced hepatitis. Journal of Immunology. 2001;166(2):1300-1307.
Wolf, D., Hallmann, R., Sass, G., Sixt, M. K., Küsters, S., Fregien, B., … Tiegs, G. (2001). TNF-α-induced expression of adhesion molecules in the liver is under the control of TNFR1--relevance for concanavalin A-induced hepatitis. Journal of Immunology, 166(2), 1300–1307.
Wolf, Dominik, Rupert Hallmann, Gabriele Sass, Michael K Sixt, Sabine Küsters, Bastian Fregien, Christian Trautwein, and Gisa Tiegs. “TNF-α-Induced Expression of Adhesion Molecules in the Liver Is under the Control of TNFR1--Relevance for Concanavalin A-Induced Hepatitis.” Journal of Immunology 166, no. 2 (2001): 1300–1307.
D. Wolf et al., “TNF-α-induced expression of adhesion molecules in the liver is under the control of TNFR1--relevance for concanavalin A-induced hepatitis,” Journal of Immunology, vol. 166, no. 2, pp. 1300–1307, 2001.
Wolf D, Hallmann R, Sass G, Sixt MK, Küsters S, Fregien B, Trautwein C, Tiegs G. 2001. TNF-α-induced expression of adhesion molecules in the liver is under the control of TNFR1--relevance for concanavalin A-induced hepatitis. Journal of Immunology. 166(2), 1300–1307.
Wolf, Dominik, et al. “TNF-α-Induced Expression of Adhesion Molecules in the Liver Is under the Control of TNFR1--Relevance for Concanavalin A-Induced Hepatitis.” Journal of Immunology, vol. 166, no. 2, American Association of Immunologists, 2001, pp. 1300–07.

Link(s) to Main File(s)
Access Level
Restricted Closed Access

Export

Marked Publications

Open Data IST Research Explorer

Search this title in

Google Scholar