| First Author | Miyata M | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6062 | PubMed ID | 25585690 |
| Mgi Jnum | J:219732 | Mgi Id | MGI:5629629 |
| Doi | 10.1038/ncomms7062 | Citation | Miyata M, et al. (2015) Glucocorticoids suppress inflammation via the upregulation of negative regulator IRAK-M. Nat Commun 6:6062 |
| abstractText | 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. |
