Serum amyloid A induces interleukin-33 expression through an IRF7-dependent pathway.
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.
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Lei
L
Sun
Ziyan
Z
Zhu
Ni
N
Cheng
Qian
Q
Yan
Richard D
RD
Ye
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D050839:Interferon Regulatory Factor-7 / Q000502:physiology*; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D000685:Serum Amyloid A Protein / Q000494:pharmacology*; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000502:physiology
C506535:Il33 protein, mouse; D050839:Interferon Regulatory Factor-7; D000067596:Interleukin-33; D007378:Interleukins; C494235:Irf7 protein, mouse; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D048029:TNF Receptor-Associated Factor 6; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2
IL-33; IRF7; Macrophages; Serum amyloid A