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- Title
- TLR3-triggered reactive oxygen species contribute to inflammatory responses by activating signal transducer and activator of transcription-1
- Author(s)
- C S Yang; J J Kim; S J Lee; Jung Hwan Hwang; Chul Ho Lee; M S Lee; E K Jo
- Bibliographic Citation
- Journal of Immunology, vol. 190, no. 12, pp. 6368-6377
- Publication Year
- 2013
- Abstract
- 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-κB, 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 p47phox) and TLR3 via a Ca2+-c-Src tyrosine kinase-dependent pathway. TLR3-induced ROS generation, NOX2, and p47phox 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 NOX2- and p47phox-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.
- ISSN
- 0022-1767
- Publisher
- Amer Assoc Immunologists
- DOI
- http://dx.doi.org/10.4049/jimmunol.1202574
- Type
- Article
- Appears in Collections:
- Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
- Files in This Item:
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