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PPAR-alpha Activation Mediates Innate Host Defense through Induction of TFEB and Lipid Catabolism
- PPAR-alpha Activation Mediates Innate Host Defense through Induction of TFEB and Lipid Catabolism
- Kim, Yi Sak; Lee, Hye-Mi; Kim, Jin Kyung; Yang, Chul-Su; Kim, Tae Sung; Jung, Mingyu; Jin, Hyo Sun; Kim, Sup; Jang, Jichan; Oh, Goo Taeg; Kim, Jin-Man; Jo, Eun-Kyeong
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- JOURNAL OF IMMUNOLOGY
- 0022-1767; 1550-6606
- vol. 198, no. 8, pp. 3283 - 3295
- AMER ASSOC IMMUNOLOGISTS
- SCI; SCIE; SCOPUS
- The role of peroxisome proliferator-activated receptor a (PPAR-alpha) in innate host defense is largely unknown. In this study, we show that PPAR-alpha is essential for antimycobacterial responses via activation of transcription factor EB (TFEB) transcription and inhibition of lipid body formation. PPAR-alpha deficiency resulted in an increased bacterial load and exaggerated inflammatory responses during mycobacterial infection. PPAR-alpha agonists promoted autophagy, lysosomal biogenesis, phagosomal maturation, and antimicrobial defense against Mycobacterium tuberculosis or M. bovis bacillus Calmette-Guerin. PPAR-alpha agonists regulated multiple genes involved in autophagy and lysosomal biogenesis, including Lamp2, Rab7, and Tfeb in bone marrow-derived macrophages. Silencing of TFEB reduced phagosomal maturation and antimicrobial responses, but increased macrophage inflammatory responses during mycobacterial infection. Moreover, PPAR-alpha activation promoted lipid catabolism and fatty acid beta-oxidation in macrophages during mycobacterial infection. Taken together, our data indicate that PPAR-alpha mediates antimicrobial responses to mycobacterial infection by inducing TFEB and lipid catabolism.
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