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Disease-Association Analysis of an Inflammation-Related Feedback Loop

Authors :
Masaaki Murakami
Masaya Harada
Daisuke Kamimura
Hideki Ogura
Yuko Okuyama
Noriko Kumai
Azusa Okuyama
Rajeev Singh
Jing-Jing Jiang
Toru Atsumi
Sayaka Shiraya
Yuji Nakatsuji
Makoto Kinoshita
Hitoshi Kohsaka
Makoto Nishida
Saburo Sakoda
Nobuyuki Miyasaka
Keiko Yamaguchi-Takihara
Toshio Hirano
Source :
Cell Reports, Vol 3, Iss 3, Pp 946-959 (2013)
Publication Year :
2013
Publisher :
Elsevier, 2013.

Abstract

The IL-6-triggered positive feedback loop for NFκB signaling (or the IL-6 amplifier/Inflammation amplifier) was originally discovered as a synergistic-activation signal that follows IL-17/IL-6 stimulation in nonimmune cells. Subsequent results from animal models have shown that the amplifier is activated by stimulation of NFκB and STAT3 and induces chemokines and inflammation via an NFκB loop. However, its role in human diseases is unclear. Here, we combined two genome-wide mouse screens with SNP-based disease association studies, revealing 1,700 genes related to the IL-6 amplifier, 202 of which showed 492 indications of association with ailments beyond autoimmune diseases. We followed up on ErbB1 from our list. Blocking ErbB1 signaling suppressed the IL-6 amplifier, whereas the expression of epiregulin, an ErbB1 ligand, was higher in patients with inflammatory diseases. These results indicate that the IL-6 amplifier is indeed associated with human diseases and disorders and that the identified genes may make for potential therapeutic targets.

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
22111247
Volume :
3
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.3e80c577c9004439a2b643e55c7d7494
Document Type :
article
Full Text :
https://doi.org/10.1016/j.celrep.2013.01.028