Endothelial Cell Gene Expression of a Neutrophil Chemotactic Factor by TNF-α, LPS, and IL-1β

• DOI: 10.1126/science.2648570
• Publication Date: 2006-10-05T21:21:28Z
• Authors: R. M. Strieter; S. L. Kunkel; H. J. Showell; D. G. Remick; S. H. Phan; P. A. Ward; R. M. Marks
• Keywords: Lipopolysaccharides; 0301 basic medicine; Time Factors; Chemotactic Factors; Tumor Necrosis Factor-alpha; Interleukin-8; In Vitro Techniques; Blotting, Northern; 3. Good health; 03 medical and health sciences; Gene Expression Regulation; Humans; Endothelium, Vascular; Oligonucleotide Probes; Interleukin-1

Human endothelial cells produced a neutrophil chemotactic factor (NCF) upon stimulation with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), or lipopolysaccharide (LPS). The expression of endothelial cell-derived NCF messenger RNA and biological activity was both time- and concentration-dependent. Maximal NCF mRNA expression occurred at 10 and at 2 nanograms per milliliter for TNF and IL-1β, respectively; mRNA expression was first observed 1 hour after stimulation and was maintained for at least 24 hours. In situ hybridization analysis showed that NCF mRNA peaked in treated cells by 24 hours, whereas unstimulated cells were negative. These studies demonstrated that endothelial cells may participate in neutrophil-mediated inflammation by synthesizing a chemotactic factor in response to specific monokines and LPS.