TLR3-triggered reactive oxygen species contribute to inflammatory responses by activating signal transducer and activator of transcription-1

Cited 55 time in scopus
Metadata Downloads
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 HwangChul 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:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.