cellular reactive oxygen species inhibit mpys induction of ifnβ细胞活性氧抑制mpy ifnβ的感应.pdfVIP

Cellular Reactive Oxygen Species Inhibit MPYS Induction of IFNb Lei Jin, Laurel L. Lenz, John C. Cambier* Integrated Department of Immunology, University of Colorado Denver School of Medicine and National Jewish Health, Denver, Colorado, United States of America Abstract Many inflammatory diseases, as well as infections, are accompanied by elevation in cellular levels of Reactive Oxygen Species (ROS). Here we report that MPYS, a.k.a. STING, which was recently shown to mediate activation of IFNb expression during infection, is a ROS sensor. ROS induce intermolecular disulfide bonds formation in MPYS homodimer and inhibit MPYS IFNb stimulatory activity. Cys-64, -148, -292, -309 and the potential C88xxC91 redox motif in MPYS are indispensable for IFNb stimulation and IRF3 activation. Thus, our results identify a novel mechanism for ROS regulation of IFNb stimulation. Citation: Jin L, Lenz LL, Cambier JC (2010) Cellular Reactive Oxygen Species Inhibit MPYS Induction of IFN b. PLoS ONE 5(12): e15142. doi:10.1371/ journal.pone.0015142 ´ Editor: Stefan Bereswill, Charite-University Medicine Berlin, Germany Received October 7, 2010; Accepted October 22, 2010; Published December 10, 2010 Copyright: 2010 Jin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by NIH 3R01AI062739-05S209 (J.C.C), 5R01AI062739-05 (J.C.C), 5R01AI065638-04 (L.L.L). J.C.C is Ida and Cecil Green Professor of Immunology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. *