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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
Author
양철수
Keywords
MYCOBACTERIUM-TUBERCULOSIS; LYSOSOMAL BIOGENESIS; PHAGOSOME MATURATION; AUTOPHAGY GENES; RECEPTOR; METABOLISM; IMMUNITY; GAMMA; INFLAMMATION; MACROPHAGES
Issue Date
2017-04
Publisher
AMER ASSOC IMMUNOLOGISTS
Citation
JOURNAL OF IMMUNOLOGY, v. 198, no. 8, page. 3283-3295
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.
URI
https://www.jimmunol.org/content/198/8/3283https://repository.hanyang.ac.kr/handle/20.500.11754/113695
ISSN
0022-1767; 1550-6606
DOI
10.4049/jimmunol.1601920
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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