View : 38 Download: 15

Small Heterodimer Partner-Targeting Therapy Inhibits Systemic Inflammatory Responses through Mitochondrial Uncoupling Protein 2

Title
Small Heterodimer Partner-Targeting Therapy Inhibits Systemic Inflammatory Responses through Mitochondrial Uncoupling Protein 2
Authors
Yang C.-S.Yuk J.-M.Kim J.-J.Hwang J.H.Lee C.-H.Kim J.-M.Oh G.T.Choi H.-S.Jo E.-K.
Ewha Authors
오구택
SCOPUS Author ID
오구택scopus
Issue Date
2013
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
vol. 8, no. 5
Indexed
SCIE; SCOPUS WOS scopus
Abstract
The orphan nuclear receptor, small heterodimer partner (SHP), appears to play a negative regulatory role in innate immune signaling. Emerging evidence warrants further study on the therapeutic targeting of SHP to suppress excessive and deleterious inflammation. Here we show that fenofibrate, which targets SHP, is required for inhibiting systemic inflammation via mitochondrial uncoupling protein 2 (UCP2). In vivo administration of fenofibrate ameliorated systemic inflammatory responses and increased survival upon experimental sepsis through SHP. An abundance of SHP was observed in mice fed fenofibrate and in cultured macrophages through LKB1-dependent activation of the AMP-activated protein kinase pathway. Fenofibrate significantly blocked endotoxin-triggered inflammatory signaling responses via SHP, but not via peroxisome proliferator-activated receptor (PPAR)-α. In addition to the known mechanism by which SHP modulates innate signaling, we identify a new role of fenofibrate-induced SHP on UCP2 induction, which is required for the suppression of inflammatory responses through modulation of mitochondrial ROS production. These data strongly suggest that the SHP-inducing drug fenofibrate paves the way for novel therapies for systemic inflammation by targeting SHP. © 2013 Yang et al.
DOI
10.1371/journal.pone.0063435
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
Files in This Item:
001.pdf(3.69 MB)Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE