| Autor: |
Harikumar, Kuzhuvelil B, Yester, Jessie W, Surace, Michael J, Oyeniran, Clement, Price, Megan M, Huang, Wei-Ching, Hait, Nitai C, Allegood, Jeremy C, Yamada, Akimitsu, Kong, Xiangqian, Lazear, Helen M, Bhardwaj, Reetika, Takabe, Kazuaki, Diamond, Michael S, Luo, Cheng, Milstien, Sheldon, Spiegel, Sarah, Kordula, Tomasz |
| Předmět: |
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| Zdroj: |
Nature Immunology; Mar2014, Vol. 15 Issue 3, p231-238, 8p, 7 Graphs |
| Abstrakt: |
Although interleukin 1 (IL-1) induces expression of the transcription factor IRF1 (interferon-regulatory factor 1), the roles of IRF1 in immune and inflammatory responses and mechanisms of its activation remain elusive. Here we found that IRF1 was essential for IL-1-induced expression of the chemokines CXCL10 and CCL5, which recruit mononuclear cells into sites of sterile inflammation. Newly synthesized IRF1 acquired Lys63 (K63)-linked polyubiquitination mediated by the apoptosis inhibitor cIAP2 that was enhanced by the bioactive lipid S1P. In response to IL-1, cIAP2 and the sphingosine kinase SphK1 (the enzyme that generates S1P) formed a complex with IRF1, which led to its activation. Thus, IL-1 triggered a hitherto unknown signaling cascade that controlled the induction of IRF1-dependent genes that encode molecules important for sterile inflammation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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