Interleukin-1 gene expression in rabbit vascular tissue in vivo

S. K. Clinton, J. C. Fleet, H. Loppnow, R. N. Salomon, B. D. Clark, Joseph Gerard Cannon, A. R. Shaw, C. A. Dinarello, P. Libby

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Abstract

Cultured human vascular endothelial and smooth muscle cells express interleukin-1 (IL-1) genes when exposed to bacterial lipopolysaccharides (LPS) and a variety of inflammatory mediators. Local production of IL-1 may contribute to the pathogenesis of various vascular diseases. Therefore the ability of intact vascular tissue to accumulate IL-1 mRNA and synthesize de novo biologically active IL-1 protein was examined. Escherichia coli LPS (10 μg/kg) was administered intravenously to adult rabbits and total RNA was isolated from aortic tissue at various times after LPS injection. In saline-injected rabbits, RNA extracted from the thoracic aorta contained little or no IL-1 message detected by Northern analysis using IL-1 α and β cDNA probes cloned from an LPS-stimulated rabbit splenic macrophage library. Lipopolysaccharide treatment promptly induced transient accumulation of mRNA for IL-1 α and IL-1 β within the aorta (maximal 1-hour after injection). Short-term organoid cultures of rabbit aorta exposed to LPS in vitro synthesized immunoprecipitable IL-1 α protein. Extracts of aortic tissue excised 1.5 to 3.0 hours after intravenous LPS administration contained immunoreactive and biologically active IL-1 α. Anti-rabbit IL-1 α antibody neutralized the biologic activity (more than 90%). Microscopic and immunohistochemical studies did not disclose adherent or infiltrating macrophages in rabbit aorta at the time of maximal IL-1 mRNA accumulation after LPS administration (1.5 hours), indicating that intrinsic vascular wall cells rather than mononuclear phagocytes probably account for the IL-1 activity induced by LPS. In addition, aortic tissue from rabbits fed an atherogenic diet showed an enhanced ability to accumulate IL-1 α and β mRNA and produce immunodetectible protein in response to LPS administration. These studies demonstrate inducible IL-1 gene expression in rabbit vascular tissue in vivo and support a local role for this cytokine in vascular pathophysiology.

Original languageEnglish (US)
Pages (from-to)1005-1014
Number of pages10
JournalAmerican Journal of Pathology
Volume138
Issue number4
StatePublished - Jan 1 1991

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Clinton, S. K., Fleet, J. C., Loppnow, H., Salomon, R. N., Clark, B. D., Cannon, J. G., Shaw, A. R., Dinarello, C. A., & Libby, P. (1991). Interleukin-1 gene expression in rabbit vascular tissue in vivo. American Journal of Pathology, 138(4), 1005-1014.