Essential Role of Induced Nitric Oxide in the Initiation of the Inflammatory Response after Hemorrhagic Shock
Open Access
- 16 March 1998
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 187 (6), 917-928
- https://doi.org/10.1084/jem.187.6.917
Abstract
Resuscitation from hemorrhagic shock induces profound changes in the physiologic processes of many tissues and activates inflammatory cascades that include the activation of stress transcriptional factors and upregulation of cytokine synthesis. This process is accompanied by acute organ damage (e.g., lungs and liver). We have previously demonstrated that the inducible nitric oxide synthase (iNOS) is expressed during hemorrhagic shock. We postulated that nitric oxide production from iNOS would participate in proinflammatory signaling. Using the iNOS inhibitor N6-(iminoethyl)-l-lysine or iNOS knockout mice we found that the activation of the transcriptional factors nuclear factor κB and signal transducer and activator of transcription 3 and increases in IL-6 and G-CSF messenger RNA levels in the lungs and livers measured 4 h after resuscitation from hemorrhagic shock were iNOS dependent. Furthermore, iNOS inhibition resulted in a marked reduction of lung and liver injury produced by hemorrhagic shock. Thus, induced nitric oxide is essential for the upregulation of the inflammatory response in resuscitated hemorrhagic shock and participates in end organ damage under these conditions.Keywords
This publication has 47 references indexed in Scilit:
- Differential Effects of Nonselective Nitric Oxide Synthase (NOS) and Selective Inducible NOS Inhibition on Hepatic Necrosis, Apoptosis, ICAM-1 Expression, and Neutrophil Accumulation during EndotoxemiaNitric Oxide, 1997
- Role of IL-6 and Its Soluble Receptor in Induction of Chemokines and Leukocyte RecruitmentImmunity, 1997
- A Molecular Redox Switch on p21Journal of Biological Chemistry, 1997
- Differential Activation of Mitogen-activated Protein Kinases by Nitric Oxide-related SpeciesJournal of Biological Chemistry, 1996
- Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthaseCell, 1995
- L-N6-(1-Iminoethyl)lysine: A Selective Inhibitor of Inducible Nitric Oxide SynthaseJournal of Medicinal Chemistry, 1994
- Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathwayCell, 1994
- A Common Nuclear Signal Transduction Pathway Activated by Growth Factor and Cytokine ReceptorsScience, 1993
- Bacterial Translocation in Trauma PatientsPublished by Wolters Kluwer Health ,1991
- Effect of hemorrhagic shock on bacterial translocation, intestinal morphology, and intestinal permeability in conventional and antibiotic-decontaminated ratsCritical Care Medicine, 1990