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PPAR-alpha Activation Mediates Innate Host Defense through Induction of TFEB and Lipid Catabolism

Title
PPAR-alpha Activation Mediates Innate Host Defense through Induction of TFEB and Lipid Catabolism
Authors
Kim, Yi SakLee, Hye-MiKim, Jin KyungYang, Chul-SuKim, Tae SungJung, MingyuJin, Hyo SunKim, SupJang, JichanOh, Goo TaegKim, Jin-ManJo, Eun-Kyeong
Ewha Authors
오구택
SCOPUS Author ID
오구택scopus
Issue Date
2017
Journal Title
JOURNAL OF IMMUNOLOGY
ISSN
0022-1767JCR Link1550-6606JCR Link
Citation
vol. 198, no. 8, pp. 3283 - 3295
Publisher
AMER ASSOC IMMUNOLOGISTS
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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.
DOI
10.4049/jimmunol.1601920
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자연과학대학 > 생명과학전공 > Journal papers
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