期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 44, 期 7, 页码 2153-2164出版社
WILEY
DOI: 10.1002/eji.201344310
关键词
IL-33; IRF7; Macrophages; Serum amyloid A
类别
资金
- National Natural Science Foundation of China [81202316, 31270941]
- National Basic Research Program of China (973 Program) [2012CB518001]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20120073110069, 20120073120092]
- U.S. National Institutes of Health [AI 033503, AI 040176]
Interleukin-33 (IL-33), an IL-1 family cytokine and nuclear alarmin, is constitutively expressed in epithelial barrier tissues and human blood vessels. However, little is known about the induced expression of IL-33 in monocytes and macrophages, which are major cytokine-producing cells of the innate immune system. Here, we report the induction of IL33 expression in both human monocytes and mouse macrophages from C57BL/6 mice by the acute-phase protein serum amyloid A (SAA). SAA-induced transcriptional activation of the Il33 gene, resulting in nuclear accumulation of the IL-33 protein. TLR2, one of the SAA receptors, was primarily responsible for the induction of IL-33. Progressive deletion of the human IL-33 promoter led to the identification of two potential binding sites for interferon regulatory factor 7 (IRF7), one of which (-277/-257) was found to be important for SAA-stimulated IL-33 promoter activity. IRF7 was recruited to the IL-33 promoter upon SAA stimulation, and silencing IRF7 expression in THP-1 cells abrogated SAA-induced Il33 expression. SAA also promoted an interaction between TNF receptor-associated factor 6 and IRF7. Taken together, these results identify IRF7 as a critical transcription factor for SAA-induced Il33 expression in monocytes and macrophages.
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