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    Peroxisome Proliferator-Activated Receptor-γ Regulates the Expression of Alveolar Macrophage Macrophage Colony- Stimulating Factor

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    Author
    Bonfield, Tracey L.; Thomassen, Mary Jane; Farver, Carol F.; Abraham, Susamma; Koloze, Mary T.; Zhang, Xia; Mosser, David M.; Culver, Daniel A.
    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.
    URI
    http://hdl.handle.net/10342/3222
    Subject
     Macrophage CSF; Peroxisome; Pulmonary alveolar proteinosis 
    Date
    2008-07-01
    Citation:
    APA:
    Bonfield, Tracey L., & Thomassen, Mary Jane, & Farver, Carol F., & Abraham, Susamma, & Koloze, Mary T., & Zhang, Xia, & Mosser, David M., & Culver, Daniel A.. (July 2008). Peroxisome Proliferator-Activated Receptor-γ Regulates the Expression of Alveolar Macrophage Macrophage Colony- Stimulating Factor. Journal of Immunology, 181(1), 235- 242. Retrieved from http://hdl.handle.net/10342/3222

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    MLA:
    Bonfield, Tracey L., and Thomassen, Mary Jane, and Farver, Carol F., and Abraham, Susamma, and Koloze, Mary T., and Zhang, Xia, and Mosser, David M., and Culver, Daniel A.. "Peroxisome Proliferator-Activated Receptor-γ Regulates the Expression of Alveolar Macrophage Macrophage Colony- Stimulating Factor". Journal of Immunology. 181:1. (235-242), July 2008. September 26, 2023. http://hdl.handle.net/10342/3222.
    Chicago:
    Bonfield, Tracey L. and Thomassen, Mary Jane and Farver, Carol F. and Abraham, Susamma and Koloze, Mary T. and Zhang, Xia and Mosser, David M. and Culver, Daniel A., "Peroxisome Proliferator-Activated Receptor-γ Regulates the Expression of Alveolar Macrophage Macrophage Colony- Stimulating Factor," Journal of Immunology 181, no. 1 (July 2008), http://hdl.handle.net/10342/3222 (accessed September 26, 2023).
    AMA:
    Bonfield, Tracey L., Thomassen, Mary Jane, Farver, Carol F., Abraham, Susamma, Koloze, Mary T., Zhang, Xia, Mosser, David M., Culver, Daniel A.. Peroxisome Proliferator-Activated Receptor-γ Regulates the Expression of Alveolar Macrophage Macrophage Colony- Stimulating Factor. Journal of Immunology. July 2008; 181(1): 235-242. http://hdl.handle.net/10342/3222. Accessed September 26, 2023.
    Collections
    • Pulmonary , Critical Care, and Sleep Medicine
    Publisher
    East Carolina University

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