Send to

Choose Destination
Nat Commun. 2015 Jan 14;6:6062. doi: 10.1038/ncomms7062.

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

Author information

Center for Inflammation, Immunity &Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30302, USA.
1] Center for Inflammation, Immunity &Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30302, USA [2] Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642, USA.
Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center, College Station, Texas 77843, USA.
Department of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

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