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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Krunkosky, TM; Fischer, BM; Akley, NJ; Adler, KB

Published Date

  • October 31, 1996

Published In

Volume / Issue

  • 796 /

Start / End Page

  • 30 - 37

PubMed ID

  • 8906209

International Standard Serial Number (ISSN)

  • 0077-8923

Language

  • eng

Conference Location

  • United States