Peroxisome Proliferator-Activated Receptor-γ Regulates the Expression of Alveolar Macrophage Macrophage Colony- Stimulating Factor
dc.contributor.author | Bonfield, Tracey L. | en_US |
dc.contributor.author | Thomassen, Mary Jane | en_US |
dc.contributor.author | Farver, Carol F. | en_US |
dc.contributor.author | Abraham, Susamma | en_US |
dc.contributor.author | Koloze, Mary T. | en_US |
dc.contributor.author | Zhang, Xia | en_US |
dc.contributor.author | Mosser, David M. | en_US |
dc.contributor.author | Culver, Daniel A. | en_US |
dc.date.accessioned | 2011-02-14T13:42:50Z | en_US |
dc.date.accessioned | 2011-05-17T01:07:45Z | |
dc.date.available | 2011-02-14T13:42:50Z | en_US |
dc.date.available | 2011-05-17T01:07:45Z | |
dc.date.issued | 2008-07-01 | en_US |
dc.description.abstract | Macrophage CSF (M-CSF) regulates monocyte differentiation, activation, and foam cell formation. We have observed that it is elevated in human pulmonary alveolar proteinosis (PAP) and in the GMCSF knockout mouse, a murine model for PAP. A potential regulator of M-CSF, peroxisome proliferator-activated receptor-γ (PPARγ), is severely deficient in both human PAP and the GM-CSF knockout mouse. To investigate the role of PPARγ in alveolar macrophage homeostasis, we generated myeloidspecific PPARγ knockout mice using the Lys-Cre method to knock out the floxed PPARγ gene. Similar to the GM-CSF-deficient mouse, absence of alveolar macrophage PPARγ resulted in development of lung pathology resembling PAP in 16-wk-old mice, along with excess M-CSF gene expression and secretion. In ex vivo wild-type alveolar macrophages, we observed that M-CSF itself is capable of inducing foam cell formation similar to that seen in PAP. Overexpression of PPARγ prevented LPS-stimulated M-CSF production in RAW 264.7 cells, an effect that was abrogated by a specific PPARγ antagonist, GW9662. Use of proteasome inhibitor, MG-132 or a PPARγ agonist, pioglitazone, prevented LPS-mediated M-CSF induction. Using chromatin immunoprecipitation, we found that PPARγ is capable of regulating M-CSF through transrepression of NF-κB binding at the promoter. Gel-shift assay experiments confirmed that pioglitazone is capable of blocking NF-κB binding. Taken together, these data suggest that M-CSF is an important mediator of alveolar macrophage homeostasis, and that transcriptional control of M-CSF production is regulated by NF-κB and PPARγ. | en_US |
dc.identifier.citation | Journal of Immunology; 181:1 p. 235-242 | en_US |
dc.identifier.pmid | PMC2819287 | en_US |
dc.identifier.uri | http://hdl.handle.net/10342/3222 | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | East Carolina University | en_US |
dc.relation.uri | http://www.jimmunol.org/content/181/1/235.long | en_US |
dc.rights | Author notified of opt-out rights by Cammie Jennings | en_US |
dc.subject | Macrophage CSF | en_US |
dc.subject | Peroxisome | en_US |
dc.subject | Pulmonary alveolar proteinosis | en_US |
dc.title | Peroxisome Proliferator-Activated Receptor-γ Regulates the Expression of Alveolar Macrophage Macrophage Colony- Stimulating Factor | en_US |
dc.type | Article | en_US |
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