Deactivation of murine alveolar macrophages by peroxisome proliferator-activated receptor-gamma ligands.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor family of ligand-dependent transcription factors, is a critical regulator of adipocyte differentiation and glucose metabolism. The expression, regulation, and functional significance of PPAR-gamma in alveolar macrophages (AMs), the predominant resident immune effector cell within the alveolus, have not been previously examined. In this study, we show that, in contrast to peritoneal macrophages, resident murine AMs constitutively express high levels of PPAR-gamma. Expression was primarily located in the nucleus by immunofluorescence staining. Quantitative real-time RT-PCR demonstrated that the predominant isoform was PPAR-gamma2. Expression of PPAR-gamma was induced by the anti-inflammatory cytokine IL-4. Treatment of murine AMs with PPAR-gamma ligands suppresses PMA-stimulated oxidative burst activity and LPS + IFN-gamma-mediated expression of inducible nitric oxide synthase. In addition, LPS-induced IL-12 mRNA and protein expression was inhibited by PPAR-gamma ligands. These results support an important immunomodulatory role for PPAR-gamma in AM responses.
Reddy
Raju C
RC
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109-0360, USA. rajuc@umich.edu
Keshamouni
Venkateshwar G
VG
Jaigirdar
Shamsul H
SH
Zeng
Xianying
X
Leff
Todd
T
Thannickal
Victor J
VJ
Standiford
Theodore J
TJ
D041721:3T3-L1 Cells; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008024:Ligands; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
C477819:15-deoxyprostaglandin J2; D016207:Cytokines; D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D015230:Prostaglandin D2