Susceptibility of cyclooxygenase-2-deficient mice to pulmonary fibrogenesis.
Journal Article (Journal Article)
The cyclooxygenase (COX)-2 enzyme has been implicated as an important mediator of pulmonary fibrosis. In this study, the lung fibrotic responses were investigated in COX-1 or COX-2-deficient (-/-) mice following vanadium pentoxide (V(2)O(5)) exposure. Lung histology was normal in saline-instilled wild-type and COX-deficient mice. COX-2(-/-), but not COX-1(-/-) or wild-type mice, exhibited severe inflammatory responses by 3 days following V(2)O(5) exposure and developed pulmonary fibrosis 2 weeks post-V(2)O(5) exposure. Western blot analysis and immunohistochemistry showed that COX-1 protein was present in type 2 epithelial cells, bronchial epithelial cells, and airway smooth muscle cells of saline or V(2)O(5)-exposed wild-type and COX-2(-/-) mice. COX-2 protein was present in Clara cells of wild-type and COX-1(-/-) terminal bronchioles and was strongly induced 24 hours after V(2)O(5) exposure. Prostaglandin (PG) E(2) levels in the bronchoalveolar lavage (BAL) fluid from wild-type and COX-1(-/-) mice were significantly up-regulated by V(2)O(5) exposure within 24 hours, whereas PGE(2) was not up-regulated in COX-2(-/-) BAL fluid. Tumor necrosis factor-alpha was elevated in the BAL fluid from all genotypes after V(2)O(5) exposure, but was significantly and chronically elevated in the BAL fluid from COX-2(-/-) mice above wild-type or COX-1(-/-) mice. These findings indicate that the COX-2 enzyme is protective against pulmonary fibrogenesis, and we suggest that COX-2 generation of PGE(2) is an important factor in resolving inflammation.
Full Text
Duke Authors
Cited Authors
- Bonner, JC; Rice, AB; Ingram, JL; Moomaw, CR; Nyska, A; Bradbury, A; Sessoms, AR; Chulada, PC; Morgan, DL; Zeldin, DC; Langenbach, R
Published Date
- August 2002
Published In
Volume / Issue
- 161 / 2
Start / End Page
- 459 - 470
PubMed ID
- 12163371
Pubmed Central ID
- PMC1850724
International Standard Serial Number (ISSN)
- 0002-9440
Digital Object Identifier (DOI)
- 10.1016/S0002-9440(10)64202-2
Language
- eng
Conference Location
- United States