IFN-gamma enhances endothelial activation induced by tumor necrosis factor but not IL-1
- PMID: 1697308
IFN-gamma enhances endothelial activation induced by tumor necrosis factor but not IL-1
Abstract
Previous studies have established that different cytokines induce distinct patterns of activation in cultured endothelial cells (EC). Treatment of EC with either TNF or IL-1 causes transient induction of endothelial leukocyte adhesion molecule-1 (ELAM-1) and a sustained increase in intercellular adhesion molecule-1 (ICAM-1) expression. TNF but not IL-1 also increases class I MHC Ag expression. IFN-gamma, which by itself increases EC class I MHC and ICAM-1 but does not induce ELAM-1 expression, has been found to act synergistically with TNF to increase class I expression. In our study, we have further examined IFN-gamma effects on both TNF and IL-1 beta responses. In contrast to IFN-gamma plus TNF cotreatment, IFN-gamma up-regulation of class I MHC molecules is not augmented by cotreatment with IL-1 beta. IFN-gamma plus TNF cotreatment synergistically increases ICAM-1 expression by 24 h of cotreatment, whereas IFN-gamma plus IL-1 beta cotreated EC show at most additive increases. IFN-gamma increases TNF-induced ELAM-1 expression such that a greater number of EC express ELAM-1 at both 4 and 24 h in the presence of IFN-gamma plus TNF compared to cultures treated with TNF alone, although the maximal level of surface expression on individual cells is not increased. Inasmuch as these times represent pre- and post-peak expression time (6 h), respectively, IFN-gamma appears both to accelerate and to prolong transient ELAM-1 expression. Although similar interactions are seen with IL-1 beta, IFN-gamma has a consistently greater effect on TNF-induced compared to IL-1-induced ELAM-1 expression. We next explored the possible mechanism(s) of the synergy between IFN-gamma and TNF. IFN-gamma and TNF do not cooperatively enhance total protein synthesis. Unexpectedly, IFN-gamma and IL-1 beta combine to depress protein synthesis, which may contribute to the failure of these cytokines to positively interact. IFN-gamma and TNF cooperatively increase ELAM-1 mRNA at 6 h and ICAM-1 mRNA at both 6 and 24 h, whereas IFN-gamma and IL-1 show markedly less cooperative augmentation of these transcripts. We conclude that IFN-gamma enhances TNF-induced EC activation by selectively and synergistically increasing synthesis of specific surface molecules, whereas IL-1-induced EC activation is largely unaffected by IFN-gamma.
Similar articles
-
IL-4 regulates endothelial cell activation by IL-1, tumor necrosis factor, or IFN-gamma.J Immunol. 1990 Aug 1;145(3):865-72. J Immunol. 1990. PMID: 1695647
-
Modulation of human endothelial cell activation by antiproliferative cytokines: exploration of arachidonic acid and intracellular cytokine pathways as possible mechanisms of action.Exp Cell Res. 1993 Jul;207(1):122-30. doi: 10.1006/excr.1993.1170. Exp Cell Res. 1993. PMID: 7686496
-
IFN-gamma regulates the expression of the adhesion molecule ELAM-1 and IL-6 production by human endothelial cells in vitro.J Immunol. 1990 Oct 1;145(7):2110-4. J Immunol. 1990. PMID: 1697876
-
[Molecular biology of adhesion molecules--structure, expression and function of ICAM-1 and ELAM-1].Nihon Rinsho. 1993 Jun;51(6):1643-9. Nihon Rinsho. 1993. PMID: 7686587 Review. Japanese.
-
Effects of tumour necrosis factor and related cytokines on vascular endothelial cells.Ciba Found Symp. 1987;131:170-84. doi: 10.1002/9780470513521.ch12. Ciba Found Symp. 1987. PMID: 3330009 Review.
Cited by
-
Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process.J Exp Med. 1994 Sep 1;180(3):995-1004. doi: 10.1084/jem.180.3.995. J Exp Med. 1994. PMID: 8064245 Free PMC article.
-
Constitutive expression of E-selectin and vascular cell adhesion molecule-1 on endothelial cells of hematopoietic tissues.Am J Pathol. 1996 Jan;148(1):165-75. Am J Pathol. 1996. PMID: 8546203 Free PMC article.
-
Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection.Nat Commun. 2025 Mar 10;16(1):2356. doi: 10.1038/s41467-025-57466-6. Nat Commun. 2025. PMID: 40064845 Free PMC article.
-
IFN-gamma amplifies NFkappaB-dependent Neisseria meningitidis invasion of epithelial cells via specific upregulation of CEA-related cell adhesion molecule 1.Cell Microbiol. 2007 Dec;9(12):2968-83. doi: 10.1111/j.1462-5822.2007.01038.x. Epub 2007 Aug 30. Cell Microbiol. 2007. PMID: 17764466 Free PMC article.
-
Endothelial activation: intracellular signaling pathways.Arthritis Res. 2002;4 Suppl 3(Suppl 3):S109-16. doi: 10.1186/ar576. Epub 2002 May 9. Arthritis Res. 2002. PMID: 12110129 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Research Materials
Miscellaneous