Role of PPARγ in COX-2 activation in mycobacterial pulmonary inflammation.
Preliminary studies show that intranasal (i.n.) administration of BCG in mice induces M1 activation of alveolar macrophages (M∅) that increase TNF-α production and cyclooxygenase-2 (COX-2) expression but reduce constitutive peroxisome proliferator-activated receptor gamma (PPARγ) expression. However, COX-2 is catalytically inactive for prostaglandin E(2) release, unlike COX-2 that is active in M1 activation in vitro by BCG. In this study, we determined the role of PPARγ for BCG-induced M1 activation in vivo and in vitro. We found that treatment of mice with GW9662, a PPARγ antagonist, prior to i.n. BCG, partially restored PPARγ expression, and decreased TNF-α production and COX-2 expression. But COX-2 was still inactive. The decreased effects on TNF-α and COX-2 were also observed when alveolar M∅ were treated in vitro with GW9662/BCG, but COX-2 was still active. Our results indicate that PPARγ upregulates M1 activation of alveolar M∅, but inactive COX-2 formation is independent of PPARγ in mycobacterial pulmonary inflammation.
College of Medicine, Florida Atlantic University, 777 Glades Rd., Boca Raton, FL 33431-0991, USA.
Mari
M
Kogiso
Tsutomu
T
Shinohara
C Kathleen
CK
Dorey
Yoshimi
Y
Shibata
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011014:Pneumonia / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D001500:BCG Vaccine; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2