TNF-alpha-induced up-regulation of intercellular adhesion molecule-1 is regulated by a Rac-ROS-dependent cascade in human airway epithelial cells
- Authors
- Kim, Hyunju; Hwang, Jung-Sun; Woo, Chang-Hoon; Kim, Eun-Young; Kim, Tae-Hee; Cho, Kyung-Jin; Seo, Ji-Min; Lee, Sang-Soo; Kim, Jae-Hong
- Issue Date
- 30-4월-2008
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- intercellular adhesion molecule-1; NF-kappa B; rac GTP-binding proteins; reactive oxygen species; respiratory mucosa; tumor necrosis factor-alpha
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.40, no.2, pp.167 - 175
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 40
- Number
- 2
- Start Page
- 167
- End Page
- 175
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/123710
- DOI
- 10.3858/emm.2008.40.2.167
- ISSN
- 1226-3613
- Abstract
- Up-regulation of intercellular adhesion molecule-1 (ICAM-1) in the lung airway epithelium is associated with the epithelium-leukocyte interaction, critical for the pathogenesis of various lung airway inflammatory diseases such as asthma. However, little is known about how ICAM-1 is up-regulated in human airway epithelial cells. In this study, we show that tumor TNF-alpha induces monocyte adhesion to A549 human lung airway epithelium and also up-regulation of ICAM-1 expression. These effects were significantly diminished by pre-treatment with diphenyliodonium (DPI), an inhibitor of NADPH oxidase-like flavoenzyme. In addition, the level of reactive oxygen species (ROS) was increased in response to TNF-alpha in A549 cells, suggesting a potential role of ROS in the TNF-alpha-induced signaling to ICAM-1 expression and monocyte adhesion to airway epithelium. Further, we found out that expression of Rac(N17), a dominant negative mutant of Rac1, suppressed TNF-alpha-induced ROS generation, ICAM-1 expression, and monocyte adhesion to airway epithelium. These findings suggest that Rac1 lies upstream of ROS generation in the TNF-alpha-induced signaling to ICAM-1 expression in airway epithelium. Finally, pretreatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappa B, reduced TNF-alpha-induced ICAM-1 expression and both DPI and Rac(N17) significantly diminished NF-kappa B activation in response to TNF-alpha. Together, we propose that Rac1-ROS-linked cascade mediate TNF-alpha-induced ICAM-1 up-regulation in the airway epithelium via NF-kappa B-dependent manner.
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- Appears in
Collections - College of Life Sciences and Biotechnology > Division of Life Sciences > 1. Journal Articles
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