Interleukin-1 gene expression in rabbit vascular tissue in vivo.
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 micrograms/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 alpha and beta cDNA probes cloned from an LPS-stimulated rabbit splenic macrophage library. Lipopolysaccharide treatment promptly induced transient accumulation of mRNA for IL-1 alpha and IL-1 beta within the aorta (maximal 1-hour after injection). Short-term organoid cultures of rabbit aorta exposed to LPS in vitro synthesized immunoprecipitable IL-1 alpha protein. Extracts of aortic tissue excised 1.5 to 3.0 hours after intravenous LPS administration contained immunoreactive and biologically active IL-1 alpha. Anti-rabbit IL-1 alpha 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 alpha and beta mRNA and produce immunodetectable 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.
Clinton
S K
SK
Dana-Farber Cancer Institute, Boston, MA 02117.
Fleet
J C
JC
Loppnow
H
H
Salomon
R N
RN
Clark
B D
BD
Cannon
J G
JG
Shaw
A R
AR
Dinarello
C A
CA
Libby
P
P
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000502:physiology; D001158:Arteries / Q000502:physiology*; D001161:Arteriosclerosis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D009924:Organ Culture Techniques; D011817:Rabbits; D011863:Radioimmunoassay; D013154:Spleen / Q000502:physiology
D007375:Interleukin-1