Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Commun. 2013;4:1684. doi: 10.1038/ncomms2674.

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

Author information

1
Center for Inflammation, Immunity & Infection and Department of Biology, Georgia State University, 100 Piedmont Avenue, Atlanta, Georgia 30303, USA.

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.

PMID:
23575688
PMCID:
PMC3644066
DOI:
10.1038/ncomms2674
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center