View : 33 Download: 8

Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD

Title
Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD
Authors
Komatsu K.Lee J.-Y.Miyata M.Hyang Lim J.Jono H.Koga T.Xu H.Yan C.Kai H.Li J.-D.
Ewha Authors
임재향
SCOPUS Author ID
임재향scopus
Issue Date
2013
Journal Title
Nature Communications
ISSN
2041-1723JCR Link
Citation
vol. 4
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The deubiquitinase CYLD acts as a key negative regulator to tightly control overactive inflammation. Most anti-inflammatory strategies have focused on directly targeting the positive regulator, which often results in significant side effects such as suppression of the host defence response. Here, we show that inhibition of phosphodiesterase 4B (PDE4B) markedly enhances upregulation of CYLD expression in response to bacteria, thereby suggesting that PDE4B acts as a negative regulator for CYLD. Interestingly, in Cyld-deficient mice, inhibition of PDE4B no longer suppresses inflammation. Moreover, PDE4B negatively regulates CYLD via specific activation of JNK2 but not JNK1. Importantly, ototopical post-inoculation administration of a PDE4 inhibitor suppresses inflammation in this animal model, thus demonstrating the therapeutic potential of targeting PDE4. These studies provide insights into how inflammation is tightly regulated via the inhibition of its negative regulator and may also lead to the development of new anti-inflammatory therapeutics that upregulate CYLD expression. © 2013 Macmillan Publishers Limited. All rights reserved.
DOI
10.1038/ncomms2674
Appears in Collections:
의과대학 > 의학과 > Journal papers
Files in This Item:
001.pdf(1.72 MB)Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

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

BROWSE