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- Publisher Website: 10.4049/jimmunol.165.7.4032
- Scopus: eid_2-s2.0-0034292434
- PMID: 11034414
- WOS: WOS:000089477500063
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Article: GM-CSF regulates bleomycin-induced pulmonary fibrosis via a prostaglandin-dependent mechanism
Title | GM-CSF regulates bleomycin-induced pulmonary fibrosis via a prostaglandin-dependent mechanism |
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Authors | |
Issue Date | 2000 |
Citation | Journal of Immunology, 2000, v. 165, n. 7, p. 4032-4039 How to Cite? |
Abstract | To characterize the role of GM-CSF in pulmonary fibrosis, we have studied bleomycin-induced fibrosis in wild-type mice vs mice with a targeted deletion of the GM-CSF gene (GM-CSF -/- mice). Without GM-CSF, pulmonary fibrosis was worse both histologically and quantitatively. These changes were not related to enhanced recruitment of inflammatory cells because wild-type and GM-CSF -/- mice recruited equivalent numbers of cells to the lung following bleomycin. Interestingly, recruitment of eosinophils was absent in GM-CSF -/- mice. We investigated whether the enhanced fibrotic response in GM-CSF -/- animals was due to a deficiency in an endogenous down-regulator of fibrogenesis. Analysis of whole lung homogenates from saline-or bleomycin-treated mice revealed that GM-CSF -/- animals had reduced levels of PGE 2 . Additionally, alveolar macrophages were harvested from wild-type and GM-CSF -/- mice that had been exposed to bleomycin. Although bleomycin treatment impaired the ability of alveolar macrophages from wild-type mice to synthesize PGE 2 , alveolar macrophages from GM-CSF -/- mice exhibited a significantly greater defect in PGE 2 synthesis than did wild-type cells. Exogenous addition of GM-CSF to alveolar macrophages reversed the PGE 2 synthesis defect in vitro. Administration of the PG synthesis inhibitor, indomethacin, to wild-type mice during the fibrogenic phase postbleomycin worsened the severity of fibrosis, implying a causal role for PGE 2 deficiency in the evolution of the fibrotic lesion. These data demonstrate that GM-CSF deficiency results in enhanced fibrogenesis in bleomycin-induced pulmonary fibrosis and indicate that one mechanism for this effect is impaired production of the potent antifibrotic eicosanoid, PGE 2 . |
Persistent Identifier | http://hdl.handle.net/10722/251593 |
ISSN | 2023 Impact Factor: 3.6 2023 SCImago Journal Rankings: 1.558 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Moore, B. B. | - |
dc.contributor.author | Coffey, M. J. | - |
dc.contributor.author | Christensen, P. | - |
dc.contributor.author | Sitterding, S. | - |
dc.contributor.author | Ngan, R. | - |
dc.contributor.author | Wilke, C. A. | - |
dc.contributor.author | McDonald, R. | - |
dc.contributor.author | Phare, S. M. | - |
dc.contributor.author | Peters-Golden, M. | - |
dc.contributor.author | Paine, R. | - |
dc.contributor.author | Toews, G. B. | - |
dc.date.accessioned | 2018-03-08T05:00:24Z | - |
dc.date.available | 2018-03-08T05:00:24Z | - |
dc.date.issued | 2000 | - |
dc.identifier.citation | Journal of Immunology, 2000, v. 165, n. 7, p. 4032-4039 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | http://hdl.handle.net/10722/251593 | - |
dc.description.abstract | To characterize the role of GM-CSF in pulmonary fibrosis, we have studied bleomycin-induced fibrosis in wild-type mice vs mice with a targeted deletion of the GM-CSF gene (GM-CSF -/- mice). Without GM-CSF, pulmonary fibrosis was worse both histologically and quantitatively. These changes were not related to enhanced recruitment of inflammatory cells because wild-type and GM-CSF -/- mice recruited equivalent numbers of cells to the lung following bleomycin. Interestingly, recruitment of eosinophils was absent in GM-CSF -/- mice. We investigated whether the enhanced fibrotic response in GM-CSF -/- animals was due to a deficiency in an endogenous down-regulator of fibrogenesis. Analysis of whole lung homogenates from saline-or bleomycin-treated mice revealed that GM-CSF -/- animals had reduced levels of PGE 2 . Additionally, alveolar macrophages were harvested from wild-type and GM-CSF -/- mice that had been exposed to bleomycin. Although bleomycin treatment impaired the ability of alveolar macrophages from wild-type mice to synthesize PGE 2 , alveolar macrophages from GM-CSF -/- mice exhibited a significantly greater defect in PGE 2 synthesis than did wild-type cells. Exogenous addition of GM-CSF to alveolar macrophages reversed the PGE 2 synthesis defect in vitro. Administration of the PG synthesis inhibitor, indomethacin, to wild-type mice during the fibrogenic phase postbleomycin worsened the severity of fibrosis, implying a causal role for PGE 2 deficiency in the evolution of the fibrotic lesion. These data demonstrate that GM-CSF deficiency results in enhanced fibrogenesis in bleomycin-induced pulmonary fibrosis and indicate that one mechanism for this effect is impaired production of the potent antifibrotic eicosanoid, PGE 2 . | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Immunology | - |
dc.title | GM-CSF regulates bleomycin-induced pulmonary fibrosis via a prostaglandin-dependent mechanism | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.4049/jimmunol.165.7.4032 | - |
dc.identifier.pmid | 11034414 | - |
dc.identifier.scopus | eid_2-s2.0-0034292434 | - |
dc.identifier.volume | 165 | - |
dc.identifier.issue | 7 | - |
dc.identifier.spage | 4032 | - |
dc.identifier.epage | 4039 | - |
dc.identifier.isi | WOS:000089477500063 | - |
dc.identifier.issnl | 0022-1767 | - |