Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Tissue-specific differences in PPARγ control of macrophage function.

ABSTRACT: PPARγ is known for its anti-inflammatory actions in macrophages. However, which macrophage populations express PPARγ in vivo and how it regulates tissue homeostasis in the steady state and during inflammation is not completely understood. We show that lung and spleen macrophages constitutively expressed PPARγ, while other macrophage populations did not. Recruitment of monocytes to sites of inflammation was associated with induction of PPARγ as they differentiated to macrophages. Its absence in these macrophages led to failed resolution of inflammation, characterized by persistent, low-level recruitment of leukocytes. Conversely, PPARγ agonists supported an earlier cessation in leukocyte recruitment during resolution of acute inflammation and likewise suppressed monocyte recruitment to chronically inflamed atherosclerotic vessels. In the steady state, PPARγ deficiency in macrophages had no obvious impact in the spleen but profoundly altered cellular lipid homeostasis in lung macrophages. Reminiscent of pulmonary alveolar proteinosis, LysM-Cre x PPARγflox/flox mice displayed mild leukocytic inflammation in the steady-state lung and succumbed faster to mortality upon infection with S. pneumoniae. Surprisingly, this mortality was not due to overly exuberant inflammation, but instead to impaired bacterial clearance. Thus, in addition to its anti-inflammatory role in promoting resolution of inflammation, PPARγ sustains functionality in lung macrophages and thereby has a pivotal role in supporting pulmonary host defense. The two major subsets of monocytes (Ly-6C+ and Ly-6Clo) from 12-week old C57Bl/6 mice were sorted and the RNA extracted and hybridized to Affymetrix GeneChip® 430 2.0 arrays. We pooled leukocytes from 5 mice for each sort and sorted 3 to 4 separate times for 3 to 4 biological replicates.

ORGANISM(S): Mus musculus

SUBMITTER: Emmanuel GAUTIER

PROVIDER: E-GEOD-32034 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Systemic analysis of PPARγ in mouse macrophage populations reveals marked diversity in expression with critical roles in resolution of inflammation and airway immunity.

Gautier Emmanuel L EL Chow Andrew A Spanbroek Rainer R Marcelin Genevieve G Greter Melanie M Jakubzick Claudia C Bogunovic Milena M Leboeuf Marylene M van Rooijen Nico N Habenicht Andreas J AJ Merad Miriam M Randolph Gwendalyn J GJ

Journal of immunology (Baltimore, Md. : 1950) 20120801 5

Although peroxisome proliferator-activated receptor γ (PPARγ) has anti-inflammatory actions in macrophages, which macrophage populations express PPARγ in vivo and how it regulates tissue homeostasis in the steady state and during inflammation remains unclear. We now show that lung and spleen macrophages selectively expressed PPARγ among resting tissue macrophages. In addition, Ly-6C(hi) monocytes recruited to an inflammatory site induced PPARγ as they differentiated to macrophages. When PPARγ wa ...[more]

PMID: 22855714

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Dataset Information

Tissue-specific differences in PPARγ control of macrophage function.

Publications

Systemic analysis of PPARγ in mouse macrophage populations reveals marked diversity in expression with critical roles in resolution of inflammation and airway immunity.

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