Glucocorticoids suppress inflammation via the upregulation of negative regulator IRAK-M

Masanori Miyata, Ji-Yun Lee, Seiko Susuki-Miyata, Wenzhuo Y. Wang, Haidong Xu, Hirofumi Kai, Koichi S. Kobayashi, Richard A. Flavell and Jian-Dong Li ()
Additional contact information
Masanori Miyata: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University
Ji-Yun Lee: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University
Seiko Susuki-Miyata: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University
Wenzhuo Y. Wang: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University
Haidong Xu: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University
Hirofumi Kai: Graduate School of Pharmaceutical Sciences, Kumamoto University
Koichi S. Kobayashi: College of Medicine, Texas A&M Health Science Center
Richard A. Flavell: Yale University School of Medicine
Jian-Dong Li: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract Glucocorticoids are among the most commonly used anti-inflammatory agents. Despite the enormous efforts in elucidating the glucocorticoid-mediated anti-inflammatory actions, how glucocorticoids tightly control overactive inflammatory response is not fully understood. Here we show that glucocorticoids suppress bacteria-induced inflammation by enhancing IRAK-M, a central negative regulator of Toll-like receptor signalling. The ability of glucocorticoids to suppress pulmonary inflammation induced by non-typeable Haemophilus influenzae is significantly attenuated in IRAK-M-deficient mice. Glucocorticoids improve the survival rate after a lethal non-typeable Haemophilus influenzae infection in wild-type mice, but not in IRAK-M-deficient mice. Moreover, we show that glucocorticoids and non-typeable Haemophilus influenzae synergistically upregulate IRAK-M expression via mutually and synergistically enhancing p65 and glucocorticoid receptor binding to the IRAK-M promoter. Together, our studies unveil a mechanism by which glucocorticoids tightly control the inflammatory response and host defense via the induction of IRAK-M and may lead to further development of anti-inflammatory therapeutic strategies.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms7062 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7062

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms7062

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().