Tumor necrosis factor alpha (TNF alpha)-induced ICAM-1 surface expression in airway epithelial cells in vitro: possible signal transduction mechanisms

• Published in: Annals of the New York Academy of Sciences Vol. 796; p. 30
• Main Authors: Krunkosky, T M, Fischer, B M, Akley, N J, Adler, K B
• Format: Journal Article
• Language: English
• Published: United States 31.10.1996
• Subjects: Adult; Antigens, CD - metabolism; Antioxidants - pharmacology; Bronchi - cytology; Bronchi - metabolism; Cell Line; Epithelium - metabolism; Flow Cytometry; Humans; Intercellular Adhesion Molecule-1 - metabolism; Protein Kinase C - metabolism; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor, Type I; Signal Transduction; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0077-8923
• DOI: 10.1111/j.1749-6632.1996.tb32564.x

Within the past several years research on the interaction of cytokines and adhesion molecules with airway epithelium in diseases has allowed us to develop a better understanding of the disease process. The cytokine, TNF alpha and the adhesion molecule ICAM-1 are important mediators in the pathogenesis of airway diseases such as asthma, chronic bronchitis, and adult respiratory distress syndrome. Effects of TNF alpha on ICAM-1 surface expression was investigated in both primary cultures of normal human bronchial epithelial (NHBE) cells and immortalized human bronchial epithelial cell line BEAS-2B. TNF alpha (0.015-150 ng/mL) significantly enhanced ICAM-1 surface expression (measured by flow cytometry) in a dose and time-dependent manner, with peak expression seen at 24 hours. This response was negated by heat inactivation of the TNF alpha prior to incubation. TNF alpha-induced ICAM-1 expression also was inhibited by pre- and coincubation of TNF alpha with 3 micrograms/mL soluble TNF-R1 or by the PKC inhibitor, Calphostin C (0.1 and 0.5 microM). The ROI scavengers, dimethylthiourea (4 mM), and dimethyl sulfoxide (0.001%), enhanced TNF alpha-induced ICAM-1 expression. Collectively, these results indicate that TNF alpha-induced ICAM-1 surface expression is a specific receptor-mediated response (TNF-R1), which is mediated by mechanisms dependent on PKC and intracellular reactive oxygen species.