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Role of PPARγ in COX-2 Activation in Mycobacterial Pulmonary Inflammation

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Abstract

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 E2 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.

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Acknowledgments

This work was supported by NIH RO1 HL71711, DOD DAMD 17-03-1-0004, Bankhead-Coley Cancer Research Program 06BS-04-9615, and the Charles E. Schmidt Biomedical Foundation (YS). The authors thank Dr. Ikuro Honda, Japan BCG Laboratory, Tokyo, for providing BCG for this study. Authors wish to thank Traci Pantuso for her technical assistance. This paper is dedicated to the memory of Ruth Ann Henriksen (Deceased April 28, 2011) whose lively intellectual exchanges will be missed.

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Authors and Affiliations

  1. College of Medicine, Florida Atlantic University, 777 Glades Rd., Boca Raton, FL, 33431-0991, USA

    Mari Kogiso, Tsutomu Shinohara & Yoshimi Shibata

  2. Virginia Tech Carilion School of Medicine and Research Institute, 3 Riverside Circle, Roanoke, VA, 24016, USA

    C. Kathleen Dorey

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  1. Mari Kogiso
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Kogiso, M., Shinohara, T., Dorey, C.K. et al. Role of PPARγ in COX-2 Activation in Mycobacterial Pulmonary Inflammation. Inflammation 35, 1685–1695 (2012). https://doi.org/10.1007/s10753-012-9486-x

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