Interleukin-1 gene expression in rabbit vascular tissue in vivo

Area of Science:

• Vascular biology
• Immunology
• Cytokine signaling

Background:

• Interleukin-1 (IL-1) is implicated in vascular disease pathogenesis.
• Vascular cells' capacity to produce IL-1 in vivo is not well understood.

Purpose of the Study:

• To investigate the inducible expression of IL-1 genes and protein synthesis in rabbit vascular tissue.
• To determine the cellular source of IL-1 in the aorta following LPS challenge.

Main Methods:

• Intravenous administration of Escherichia coli lipopolysaccharides (LPS) to rabbits.
• Isolation of aortic RNA for Northern analysis of IL-1 alpha and beta mRNA.
• Organoid culture of rabbit aorta with LPS exposure.
• Immunoprecipitation and bioassays for IL-1 alpha protein detection.
• Microscopic and immunohistochemical analysis of aortic tissue.

Main Results:

• LPS induced transient accumulation of IL-1 alpha and beta mRNA in rabbit aorta within 1 hour.
• Rabbit aortic organ cultures synthesized immunoprecipitable IL-1 alpha protein upon LPS exposure.
• Biologically active IL-1 alpha protein was detected in aortic tissue 1.5-3.0 hours post-LPS.
• Intrinsic vascular wall cells, not macrophages, were identified as the likely source of LPS-induced IL-1.
• Atherogenic diet-fed rabbits showed enhanced IL-1 mRNA and protein response to LPS.

Conclusions:

• Vascular tissue in rabbits can be induced to express IL-1 genes and synthesize IL-1 protein in response to LPS.
• Local IL-1 production by vascular cells may play a significant role in vascular pathophysiology.
• Findings support a local inflammatory role for IL-1 in the development of vascular diseases.