Glucocorticoids suppress inflammation via the upregulation of negative regulator IRAK-M.
Glucocorticoids suppress inflammation via the upregulation of negative regulator IRAK-M.
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DOI：
10.1038/ncomms7062
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发表时间：
2015-01-14
影响因子：
16.6
通讯作者：
Li, Jian-Dong
中科院分区：
文献类型：
--
作者：
Miyata, Masanori;Lee, Ji-Yun;Susuki-Miyata, Seiko;Wang, Wenzhuo Y.;Xu, Haidong;Kai, Hirofumi;Kobayashi, Koichi S.;Flavell, Richard A.;Li, Jian-Dong
糖皮质激素是最常用的抗炎药之一。尽管在阐明糖皮质激素介导的抗炎作用方面做出了巨大努力，但糖皮质激素如何严格控制过度活跃的炎症反应尚未完全了解。在这里，我们表明，糖皮质激素通过增强IRAK-M抑制细菌诱导的炎症，IRAK-M是Toll样受体信号传导的中枢负调节因子。糖皮质激素抑制由不可分型流感嗜血杆菌诱导的肺部炎症的能力在IRAK-M缺陷小鼠中显著减弱。糖皮质激素可提高野生型小鼠感染致死性非分型流感嗜血杆菌后的存活率，但对IRAK-M缺陷型小鼠无效。此外，我们表明，糖皮质激素和非分型流感嗜血杆菌协同上调IRAK-M的表达，通过相互和协同增强p65和糖皮质激素受体结合IRAK-M启动子。总之，我们的研究揭示了糖皮质激素通过诱导IRAK-M严格控制炎症反应和宿主防御的机制，并可能导致抗炎治疗策略的进一步发展。 糖皮质激素强烈抑制炎症。在这里，作者表明，这种抑制是通过诱导负性炎症调节因子IRAK-M介导的，并证明了其在宿主防御肺炎病原菌（不可分型流感嗜血杆菌）中的重要作用。
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. Glucocorticoids strongly suppress inflammation. Here the authors show that this suppression is mediated by induction of the negative inflammatory regulator IRAK-M, and demonstrate its important role in host defense against the pneumonia-causative bacterium, non-typeable Haemophilus influenzae.
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影响因子：
4.9
作者：
Berglund, Martin;Melgar, Silvia;Hultgren, Olof H.
通讯作者：
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Taubman, Mark B.
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Cidlowski JA
影响因子：
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Johannessen, Cory M.;Boehm, Jesse S.;Kim, So Young;Thomas, Sapana R.;Wardwell, Leslie;Johnson, Laura A.;Emery, Caroline M.;Stransky, Nicolas;Cogdill, Alexandria P.;Barretina, Jordi;Caponigro, Giordano;Hieronymus, Haley;Murray, Ryan R.;Salehi-Ashtiani, Kourosh;Hill, David E.;Vidal, Marc;Zhao, Jean J.;Yang, Xiaoping;Alkan, Ozan;Kim, Sungjoon;Harris, Jennifer L.;Wilson, Christopher J.;Myer, Vic E.;Finan, Peter M.;Root, David E.;Roberts, Thomas M.;Golub, Todd;Flaherty, Keith T.;Dummer, Reinhard;Weber, Barbara L.;Sellers, William R.;Schlegel, Robert;Wargo, Jennifer A.;Hahn, William C.;Garraway, Levi A.
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Garraway, Levi A.