期刊
JOURNAL OF IMMUNOLOGY
卷 190, 期 12, 页码 6368-6377出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1202574
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资金
- National Research Foundation of Korea
- Korean Ministry of Science and Technology through Infection Signaling Network Research Center at Chungnam National University [2007-0054932]
- Korea Research Institute of Bioscience and Biotechnology Research Initiative Program
- National Research Foundation of Korea [2007-0054932] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Intracellular reactive oxygen species (ROS) are essential secondary messengers in many signaling cascades governing innate immunity and cellular functions. TLR3 signaling is crucially involved in antiviral innate and inflammatory responses; however, the roles of ROS in TLR3 signaling remain largely unknown. In this study, we show that TLR3-induced ROS generation is required for the activation of NF-kappa B, IFN-regulatory factor 3, and STAT1-mediated innate immune responses in macrophages. TLR3 induction led to a rapid increase in ROS generation and a physical association between components of the NADPH oxidase (NOX) enzyme complex (NOX2 and p47(phox)) and TLR3 via a Ca2+ -c-Src tyrosine kinase-dependent pathway. TLR3-induced ROS generation, NOX2- and p47(phox) were required for the phosphorylation and nuclear translocation of STAT1 and STAT2. TLR3-induced activation of STAT1 contributed to the generation of inflammatory mediators, which was significantly attenuated in NOX2and p47(phox) -deficient macrophages, suggesting a role for ROS-STAT1 in TLR3-mediated innate immune responses. Collectively, these results provide a novel insight into the crucial role that TLR3-ROS signaling plays in innate immune responses by activating STAT1.
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