Endothelial Cell Gene Expression of a Neutrophil Chemotactic Factor by TNF-$\alpha $, LPS, and IL-1$\beta

• Published in: Science (American Association for the Advancement of Science) 1989-03, Vol.243 (4897), p.1467-1469
• Main Authors: Strieter, R. M., Kunkel, S. L., Showell, H. J., Remick, D. G., Phan, S. H., Ward, P. A., Marks, R. M.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood; Blotting, Northern; Chemotactic factors; Chemotactic Factors - genetics; Chemotaxis; Cytokines; Endothelial cells; Endothelium; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation - drug effects; Human umbilical vein endothelial cells; Humans; Immune response; In situ hybridization; In Vitro Techniques; Interleukin-1 - pharmacology; Interleukin-8; Lasers; Lipopolysaccharides - pharmacology; Messenger RNA; Molecular and cellular biology; Molecular genetics; Neutrophils; Oligonucleotide Probes; RNA; Time Factors; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2648570

Human endothelial cells produced a neutrophil chemotactic factor (NCF) upon stimulation with tumor necrosis factor--$\alpha $ (TNF-$\alpha $), interleukin-1$\beta $ (IL-1$\beta $), or lipopolysaccharide (LPS). The expression of endothelial cell-derived NCF messenger RNA and biological activity was both time- and concentration-dependent. Maximal NCF mRNA expression occurred at 10 and at 2 nanograms per milliliter for TNF and IL-1$\beta $, 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.