Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells

Area of Science:

• Immunology
• Cell Biology
• Vascular Biology

Background:

• Interleukin 1 (IL-1) is a key mediator involved in inflammatory responses and can induce pathogenic functions in vascular endothelial cells.
• IL-1 production was traditionally attributed primarily to activated macrophages.

Purpose of the Study:

• To investigate the capacity of adult human vascular endothelial cells to produce Interleukin 1 (IL-1).
• To determine if endothelial cells express IL-1 mRNA and protein in response to inflammatory stimuli.

Main Methods:

• Adult human vascular endothelial cells were stimulated with bacterial endotoxin and recombinant human tumor necrosis factor.
• Messenger RNA (mRNA) accumulation for IL-1 beta and IL-1 alpha was assessed.
• Metabolic labeling and immunoprecipitation were used to detect IL-1 protein synthesis and secretion.
• Biological activity of released IL-1 was confirmed using neutralization assays with anti-IL-1 antibody.

Main Results:

• Bacterial endotoxin and tumor necrosis factor induced accumulation of IL-1 beta mRNA in endothelial cells.
• IL-1 alpha mRNA was detected under superinduction conditions with cycloheximide.
• Endothelial cells synthesized and secreted biologically active IL-1 protein, comparable to monocyte-derived IL-1.
• The released IL-1 exhibited biological activity and was neutralized by specific antibodies.

Conclusions:

• Adult human vascular endothelial cells are a significant source of IL-1, challenging previous assumptions.
• Endothelial IL-1 production, triggered by microbial products or injury, may initiate local inflammatory responses.
• This autocrine mechanism in endothelial cells could contribute to the pathogenesis of vascular diseases like vasculitis, allograft rejection, and arteriosclerosis.