Cell Reports (Jul 2017)
Positive Regulation of Interleukin-1β Bioactivity by Physiological ROS-Mediated Cysteine S-Glutathionylation
- Xue Zhang,
- Peng Liu,
- Christie Zhang,
- Direkrit Chiewchengchol,
- Fan Zhao,
- Hongbo Yu,
- Jingyu Li,
- Hiroto Kambara,
- Kate Y. Luo,
- Arvind Venkataraman,
- Ziling Zhou,
- Weidong Zhou,
- Haiyan Zhu,
- Li Zhao,
- Jiro Sakai,
- Yuanyuan Chen,
- Ye-Shih Ho,
- Besnik Bajrami,
- Bing Xu,
- Leslie E. Silberstein,
- Tao Cheng,
- Yuanfu Xu,
- Yuehai Ke,
- Hongbo R. Luo
Affiliations
- Xue Zhang
- Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China
- Peng Liu
- The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China
- Christie Zhang
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- Direkrit Chiewchengchol
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- Fan Zhao
- The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China
- Hongbo Yu
- Hematopathology, Flow Cytometry, Hematology, and Blood Bank Labs, VA Boston Healthcare System, West Roxbury, MA 02132, USA
- Jingyu Li
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- Hiroto Kambara
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- Kate Y. Luo
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- Arvind Venkataraman
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- Ziling Zhou
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- Weidong Zhou
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA
- Haiyan Zhu
- The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China
- Li Zhao
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- Jiro Sakai
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- Yuanyuan Chen
- Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China
- Ye-Shih Ho
- Institute of Environmental Health Sciences and Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, MI 48201, USA
- Besnik Bajrami
- Mass Spectrometry Unit, Waters Corporation, Milford, MA 01757, USA
- Bing Xu
- Department of Chemistry, Brandeis University, 415 South Street MS015, Waltham, MA 02454, USA
- Leslie E. Silberstein
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- Tao Cheng
- The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China
- Yuanfu Xu
- The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China
- Yuehai Ke
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- Hongbo R. Luo
- Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- DOI
- https://doi.org/10.1016/j.celrep.2017.05.070
- Journal volume & issue
-
Vol. 20,
no. 1
pp. 224 – 235
Abstract
Reactive oxygen species (ROS)-induced cysteine S-glutathionylation is an important posttranslational modification (PTM) that controls a wide range of intracellular protein activities. However, whether physiological ROS can modulate the function of extracellular components via S-glutathionylation is unknown. Using a screening approach, we identified ROS-mediated cysteine S-glutathionylation on several extracellular cytokines. Glutathionylation of the highly conserved Cys-188 in IL-1β positively regulates its bioactivity by preventing its ROS-induced irreversible oxidation, including sulfinic acid and sulfonic acid formation. We show this mechanism protects IL-1β from deactivation by ROS in an in vivo system of irradiation-induced bone marrow (BM) injury. Glutaredoxin 1 (Grx1), an enzyme that catalyzes deglutathionylation, was present and active in the extracellular space in serum and the BM, physiologically regulating IL-1β glutathionylation and bioactivity. Collectively, we identify cysteine S-glutathionylation as a cytokine regulatory mechanism that could be a therapeutic target in the treatment of various infectious and inflammatory diseases.
Keywords
- cytokines
- interleukin-1
- oxidation
- infection and inflammation
- reactive oxygen species
- posttranslational modification
- cysteine S-glutathionylation
