Your browser doesn't support javascript.
loading
NRROS negatively regulates reactive oxygen species during host defence and autoimmunity.
Noubade, Rajkumar; Wong, Kit; Ota, Naruhisa; Rutz, Sascha; Eidenschenk, Celine; Valdez, Patricia A; Ding, Jiabing; Peng, Ivan; Sebrell, Andrew; Caplazi, Patrick; DeVoss, Jason; Soriano, Robert H; Sai, Tao; Lu, Rongze; Modrusan, Zora; Hackney, Jason; Ouyang, Wenjun.
Afiliación
  • Noubade R; 1] Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA [2] Flexus Biosciences, 75 Shoreway Road, Suite D, San Carlos, California 94070, USA (R.N.); American Society for Biochemistry and Molecular Biology, 11200 Rockville Pike, Suite 302, Rockville, Marylan
  • Wong K; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Ota N; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Rutz S; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Eidenschenk C; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Valdez PA; 1] Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA [2] Flexus Biosciences, 75 Shoreway Road, Suite D, San Carlos, California 94070, USA (R.N.); American Society for Biochemistry and Molecular Biology, 11200 Rockville Pike, Suite 302, Rockville, Marylan
  • Ding J; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Peng I; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Sebrell A; Department of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Caplazi P; Department of Pathology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • DeVoss J; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Soriano RH; Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Sai T; Department of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Lu R; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Modrusan Z; Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Hackney J; Department of Bioinformatics, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
  • Ouyang W; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Nature ; 509(7499): 235-9, 2014 May 08.
Article en En | MEDLINE | ID: mdl-24739962
Reactive oxygen species (ROS) produced by phagocytes are essential for host defence against bacterial and fungal infections. Individuals with defective ROS production machinery develop chronic granulomatous disease. Conversely, excessive ROS can cause collateral tissue damage during inflammatory processes and therefore needs to be tightly regulated. Here we describe a protein, we termed negative regulator of ROS (NRROS), which limits ROS generation by phagocytes during inflammatory responses. NRROS expression in phagocytes can be repressed by inflammatory signals. NRROS-deficient phagocytes produce increased ROS upon inflammatory challenges, and mice lacking NRROS in their phagocytes show enhanced bactericidal activity against Escherichia coli and Listeria monocytogenes. Conversely, these mice develop severe experimental autoimmune encephalomyelitis owing to oxidative tissue damage in the central nervous system. Mechanistically, NRROS is localized to the endoplasmic reticulum, where it directly interacts with nascent NOX2 (also known as gp91(phox) and encoded by Cybb) monomer, one of the membrane-bound subunits of the NADPH oxidase complex, and facilitates the degradation of NOX2 through the endoplasmic-reticulum-associated degradation pathway. Thus, NRROS provides a hitherto undefined mechanism for regulating ROS production--one that enables phagocytes to produce higher amounts of ROS, if required to control invading pathogens, while minimizing unwanted collateral tissue damage.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas / Especies Reactivas de Oxígeno / Encefalomielitis Autoinmune Experimental / Escherichia coli / Listeria monocytogenes Límite: Animals Idioma: En Revista: Nature Año: 2014 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas / Especies Reactivas de Oxígeno / Encefalomielitis Autoinmune Experimental / Escherichia coli / Listeria monocytogenes Límite: Animals Idioma: En Revista: Nature Año: 2014 Tipo del documento: Article