The Journal of Immunology, Vol 139, Issue 6 1911-1917, Copyright © 1987 by American Association of Immunologists

ARTICLES

Interleukin 1 induces interleukin 1. II. Recombinant human interleukin 1 induces interleukin 1 production by adult human vascular endothelial cells

SJ Warner, KR Auger and P Libby

Interleukin 1 (IL-1) alters several potentially pathogenic endothelial cell (EC) functions. The authors report here that recombinant human IL- 1 (rIL-1) alpha (0.1 to 10 ng/ml) or IL-1-beta (1 to 100 ng/ml) induce concentration- and time-dependent increases in IL-1-beta mRNA levels in EC derived from adult human saphenous vein. rIL-1 induced IL-1-alpha mRNA only in EC treated concomitantly with cycloheximide (2 micrograms/ml). IL-1-beta mRNA production began within 1 hr of exposure to rIL-1, peaked after 24 hr, and declined thereafter. Actinomycin D prevented the appearance of IL-1 mRNA in rIL-1-treated EC. rIL-1 also induced the release of biologically active IL-1 from EC, which was inhibited by cycloheximide (1 microgram/ml). When compared on the basis of their activity in the thymocyte costimulation assay, rIL-1-alpha and rIL-1-beta were equipotent as inducers of IL-1 production by EC. EC stimulated with rIL-1 produced prostaglandin E2, which inhibits IL-1 production by other cell types and also decreases the responsiveness of thymocytes to IL-1. When EC were exposed to rIL-1 in the presence of indomethacin (1 microgram/ml), which blocked prostaglandin E2 production, greater amounts of rIL-1-induced IL-1 release were detected, although the inhibitor did not affect IL-1-beta mRNA levels. IL-1-induced IL-1 production was unlikely to be caused by endotoxin contamination of tissue culture media or IL-1 preparations, because the lipopolysaccharide (LPS) antagonist polymyxin B (10 micrograms/ml) blocked LPS-induced IL-1 production by EC but did not affect IL-1 release in response to rIL-1-beta (100 ng/ml). The IL-1-inducing property of rIL-1-beta was heat-labile, whereas heated LPS stimulated EC IL-1 production. The source of IL-1 in our cultures was not monocyte/macrophages, as treatment of EC with monoclonal antibody to the monocyte antigen Mo2 under conditions that lysed adherent peripheral blood monocytes did not affect production of IL-1 by EC in response to LPS (1 microgram/ml) or rIL-1-beta (100 ng/ml). IL-1 elicits a coordinated program of altered endothelial function that increases adhesiveness for leukocytes and coagulability. IL-1-induced IL-1 gene expression in human adult EC could thus provide a positive feedback mechanism in the pathogenesis of vascular disease including atherosclerosis, vasculitis, and allograft rejection.

This article has been cited by other articles:

				G. J. Brunn, S. Saadi, and J. L. Platt Constitutive Repression of Interleukin-1{alpha} in Endothelial Cells Circ. Res., April 11, 2008; 102(7): 823 - 830. [Abstract] [Full Text] [PDF]

				H. Loppnow, K. Werdan, and M. Buerke Invited review: Vascular cells contribute to atherosclerosis by cytokine- and innate-immunity-related inflammatory mechanisms Innate Immunity, April 1, 2008; 14(2): 63 - 87. [Abstract] [PDF]

				K. Shchors, E. Shchors, F. Rostker, E. R. Lawlor, L. Brown-Swigart, and G. I. Evan The Myc-dependent angiogenic switch in tumors is mediated by interleukin 1beta Genes & Dev., September 15, 2006; 20(18): 2527 - 2538. [Abstract] [Full Text] [PDF]

				A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]

				G. J. Brunn, S. Saadi, and J. L. Platt Differential Regulation of Endothelial Cell Activation by Complement and Interleukin 1{alpha} Circ. Res., March 31, 2006; 98(6): 793 - 800. [Abstract] [Full Text] [PDF]

				D. Chida, T. Imaki, T. Suda, and Y. Iwakura Involvement of Corticotropin-Releasing Hormone- and Interleukin (IL)-6-Dependent Proopiomelanocortin Induction in the Anterior Pituitary during Hypothalamic-Pituitary-Adrenal Axis Activation by IL-1{alpha} Endocrinology, December 1, 2005; 146(12): 5496 - 5502. [Abstract] [Full Text] [PDF]

				G. K. Hansson ATVB In Focus: Immunity and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 17 - 17. [Full Text] [PDF]

				V. M. Irikura, M. Lagraoui, and D. Hirsh The Epistatic Interrelationships of IL-1, IL-1 Receptor Antagonist, and the Type I IL-1 Receptor J. Immunol., July 1, 2002; 169(1): 393 - 398. [Abstract] [Full Text] [PDF]

				K. E. Willet, B. W. Kramer, S. G. Kallapur, M. Ikegami, J. P. Newnham, T. J. Moss, P. D. Sly, and A. H. Jobe Pre- and Postnatal Lung Development, Maturation, and Plasticity: Intra-amniotic injection of IL-1 induces inflammation and maturation in fetal sheep lung Am J Physiol Lung Cell Mol Physiol, March 1, 2002; 282(3): L411 - L420. [Abstract] [Full Text] [PDF]

				Y. Toda, J. Tsukada, M. Misago, Y. Kominato, P. E. Auron, and Y. Tanaka Autocrine Induction of the Human Pro-IL-1{beta} Gene Promoter by IL-1{beta} in Monocytes J. Immunol., February 15, 2002; 168(4): 1984 - 1991. [Abstract] [Full Text] [PDF]

				G. K. Hansson Immune Mechanisms in Atherosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 2001; 21(12): 1876 - 1890. [Abstract] [Full Text] [PDF]

				G. Valen, Z.-q. Yan, and G.o. K. Hansson Nuclear factor kappa-B and the heart J. Am. Coll. Cardiol., August 1, 2001; 38(2): 307 - 314. [Abstract] [Full Text] [PDF]

				T. Takahashi, F. Hato, T. Yamane, H. Fukumasu, K. Suzuki, S. Ogita, Y. Nishizawa, and S. Kitagawa Activation of Human Neutrophil by Cytokine-Activated Endothelial Cells Circ. Res., March 2, 2001; 88(4): 422 - 429. [Abstract] [Full Text] [PDF]

				S. Saadi, R. A. Holzknecht, C. P. Patte, and J. L. Platt Endothelial Cell Activation by Pore-Forming Structures : Pivotal Role for Interleukin-1{alpha} Circulation, April 18, 2000; 101(15): 1867 - 1873. [Abstract] [Full Text] [PDF]

				J. Chamberlain, J. Gunn, S. Francis, C. Holt, and D. Crossman Temporal and spatial distribution of interleukin-1{beta} in balloon injured porcine coronary arteries Cardiovasc Res, October 1, 1999; 44(1): 156 - 165. [Abstract] [Full Text] [PDF]

				J. Dumin, B. D. Wilcox, I. Otterness, J. A. Melendez, C. Huang, and J. J. Jeffrey Serotonin-mediated Production of Interstitial Collagenase by Uterine Smooth Muscle Cells Requires Interleukin-1alpha , but not Interleukin-1beta J. Biol. Chem., September 25, 1998; 273(39): 25488 - 25494. [Abstract] [Full Text] [PDF]

				Y.-H. Tseng and L. A. Schuler Transcriptional Regulation of Interleukin-1beta Gene by Interleukin-1beta Itself Is Mediated in Part by Oct-1 in Thymic Stromal Cells J. Biol. Chem., May 15, 1998; 273(20): 12633 - 12641. [Abstract] [Full Text] [PDF]

				R. De Caterina, W. Bernini, M. A. Carluccio, J. K. Liao, and P. Libby Structural requirements for inhibition of cytokine-induced endothelial activation by unsaturated fatty acids J. Lipid Res., May 1, 1998; 39(5): 1062 - 1070. [Abstract] [Full Text]

				E M Nilsen, F-E Johansen, F L Jahnsen, K E A Lundin, T Scholz, P Brandtzaeg, and G Haraldsen Cytokine profiles of cultured microvascular endothelial cells from the human intestine Gut, May 1, 1998; 42(5): 635 - 642. [Abstract] [Full Text] [PDF]

				U. Schonbeck, F. Mach, J.-Y. Bonnefoy, H. Loppnow, H.-D. Flad, and P. Libby Ligation of CD40 Activates Interleukin 1beta -converting Enzyme (Caspase-1) Activity in Vascular Smooth Muscle and Endothelial Cells and Promotes Elaboration of Active Interleukin 1beta J. Biol. Chem., August 1, 1997; 272(31): 19569 - 19574. [Abstract] [Full Text] [PDF]

				J. Galea, J. Armstrong, P. Gadsdon, H. Holden, S. E. Francis, and C. M. Holt Interleukin-1ß in Coronary Arteries of Patients With Ischemic Heart Disease Arterioscler. Thromb. Vasc. Biol., August 1, 1996; 16(8): 1000 - 1006. [Abstract] [Full Text]

				R. Kranzhofer, S. K. Clinton, K. Ishii, S. R. Coughlin, J. W. Fenton, and P. Libby Thrombin Potently Stimulates Cytokine Production in Human Vascular Smooth Muscle Cells but Not in Mononuclear Phagocytes Circ. Res., August 1, 1996; 79(2): 286 - 294. [Abstract] [Full Text]