Abstract
We investigated the effects of mechanical stretch and induced stimulation of lung parenchyma on the activation of proinflammatory transcription factors in normal mice and in a mouse model of asthma. Mechanical stretching of lung parenchyma led to increased activation of NF-κB and AP-1 transcription factors. Incubation of lung parenchyma with methacholine increased the activation of NF-κB, which was further augmented by stretch. Activation of NF-κB in response to mechanical stretch was associated with the phosphorylation and degradation of IκBα and the activation of IκB kinase. Stretch-induced activation of NF-κB involves activation of stretch-activated (SA) channels and the production of free radicals. Mechanical stretch and/or treatment with methacholine resulted in an increased activation of ERK1/2 and p38 MAP kinase, and the inhibition of the activity of these kinases partially blocked the stretch-induced NF-κB and AP-1 activation. A greater level of NF-κB and ERK1/2 activity was observed in the asthmatic mice, which was further increased by mechanical stretching. The level of cyclooxygenase-2, an NF-κB-regulated enzyme, was also higher in lung parenchyma from asthmatic mice than in normal mice. Our data suggest that mechanical stretching of lung parenchyma activates NF-κB and AP-1, at least in part, through the activation of MAP kinase signaling pathways.
Original language | English (US) |
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Pages (from-to) | 1800-1811 |
Number of pages | 12 |
Journal | FASEB Journal |
Volume | 17 |
Issue number | 13 |
DOIs | |
State | Published - Oct 1 2003 |
Keywords
- Activator protein-1
- Asthma
- Cyclooxygenase-2
- Free radicals
- Lung mechanics
- MAP kinases
- Mechanotransduction
- Nuclear factor-kappaB
- Stretch-activated channels
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Cell Biology