The Peroxisome Proliferator-Activated Receptor α- Agonist Gemfibrozil Promotes Defense Against Mycobacterium abscessus Infections.

Cells
Yi Sak KimEun-Kyeong Jo

Abstract

Peroxisome proliferator-activated receptor α (PPARα) shows promising potential to enhance host defenses against Mycobacterium tuberculosis infection. Herein we evaluated the protective effect of PPARα against nontuberculous mycobacterial (NTM) infections. Using a rapidly growing NTM species, Mycobacterium abscessus (Mabc), we found that the intracellular bacterial load and histopathological damage were increased in PPARα-null mice in vivo. In addition, PPARα deficiency led to excessive production of proinflammatory cytokines and chemokines after infection of the lung and macrophages. Notably, administration of gemfibrozil (GEM), a PPARα activator, significantly reduced the in vivo Mabc load and inflammatory response in mice. Transcription factor EB was required for the antimicrobial response against Mabc infection. Collectively, these results suggest that manipulation of PPARα activation has promising potential as a therapeutic strategy for NTM disease.

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Citations

Sep 2, 2020·Cells·Prashanta SilwalEun-Kyeong Jo
Jan 22, 2021·Experimental & Molecular Medicine·Hyeon Ji KimEun-Kyeong Jo
Jul 25, 2021·International Journal of Molecular Sciences·Kazunari TanigawaKoichi Suzuki

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Methods Mentioned

BETA
nuclear translocation
PCR
ELISA
Assay

Software Mentioned

GraphPad Prism
MetaMorph Advanced Imaging
GraphPad

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