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-α 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-α in A549 cells, suggesting a potential role of ROS in the TNF-α-induced signaling to ICAM-1 expression and monocyte adhesion to airway epithelium. Further, we found out that expression of RacN17, a dominant negative mutant of Rac1, suppressed TNF-α-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-α-induced signaling to ICAM-1 expression in airway epithelium. Finally, pretreatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, reduced TNF-α-induced ICAM-1 expression and both DPI and RacN17 significantly diminished NF-κB activation in response to TNF-α. Together, we propose that Rac1-ROS-linked cascade mediate TNF-α-induced ICAM-1 up-regulation in the airway epithelium via NF-κB-dependent manner.
| Original language | English |
|---|---|
| Pages (from-to) | 167-175 |
| Number of pages | 9 |
| Journal | Experimental and Molecular Medicine |
| Volume | 40 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2008 Apr 30 |
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Keywords
- Intercellular adhesion molecule-1
- NF-κB
- Rac GTP-binding proteins
- Reactive oxygen species
- Respiratory mucosa
- Tumor necrosis factor-α
ASJC Scopus subject areas
- Biochemistry
- Genetics
Cite this
TNF-α-induced up-regulation of intercellular adhesion molecule-1 is regulated by a Rac-ROS-dependent cascade in human airway epithelial cells. / 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.
In: Experimental and Molecular Medicine, Vol. 40, No. 2, 30.04.2008, p. 167-175.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TNF-α-induced up-regulation of intercellular adhesion molecule-1 is regulated by a Rac-ROS-dependent cascade in human airway epithelial cells
AU - Kim, Hyunju
AU - Hwang, Jung Sun
AU - Woo, Chang Hoon
AU - Kim, Eun Young
AU - Kim, Tae Hee
AU - Cho, Kyung Jin
AU - Seo, Ji Min
AU - Lee, Sang Soo
AU - Kim, Jae-Hong
PY - 2008/4/30
Y1 - 2008/4/30
N2 - 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-α 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-α in A549 cells, suggesting a potential role of ROS in the TNF-α-induced signaling to ICAM-1 expression and monocyte adhesion to airway epithelium. Further, we found out that expression of RacN17, a dominant negative mutant of Rac1, suppressed TNF-α-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-α-induced signaling to ICAM-1 expression in airway epithelium. Finally, pretreatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, reduced TNF-α-induced ICAM-1 expression and both DPI and RacN17 significantly diminished NF-κB activation in response to TNF-α. Together, we propose that Rac1-ROS-linked cascade mediate TNF-α-induced ICAM-1 up-regulation in the airway epithelium via NF-κB-dependent manner.
AB - 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-α 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-α in A549 cells, suggesting a potential role of ROS in the TNF-α-induced signaling to ICAM-1 expression and monocyte adhesion to airway epithelium. Further, we found out that expression of RacN17, a dominant negative mutant of Rac1, suppressed TNF-α-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-α-induced signaling to ICAM-1 expression in airway epithelium. Finally, pretreatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, reduced TNF-α-induced ICAM-1 expression and both DPI and RacN17 significantly diminished NF-κB activation in response to TNF-α. Together, we propose that Rac1-ROS-linked cascade mediate TNF-α-induced ICAM-1 up-regulation in the airway epithelium via NF-κB-dependent manner.
KW - Intercellular adhesion molecule-1
KW - NF-κB
KW - Rac GTP-binding proteins
KW - Reactive oxygen species
KW - Respiratory mucosa
KW - Tumor necrosis factor-α
UR - http://www.scopus.com/inward/record.url?scp=44349089740&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44349089740&partnerID=8YFLogxK
U2 - 10.3858/emm.2008.40.2.167
DO - 10.3858/emm.2008.40.2.167
M3 - Article
VL - 40
SP - 167
EP - 175
JO - Experimental and Molecular Medicine
JF - Experimental and Molecular Medicine
SN - 1226-3613
IS - 2
ER -