Extracellular superoxide dismutase is upregulated with inducible nitric oxide synthase after NF-κB activation

1997 ◽  
Vol 273 (5) ◽  
pp. L1002-L1006 ◽  
Author(s):  
Todd C. Brady ◽  
Ling-Yi Chang ◽  
Brian J. Day ◽  
James D. Crapo
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Dermal Fibroblasts ◽  
Extracellular Superoxide Dismutase ◽  
Tnf Α ◽  
Ifn Γ ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Inflammatory cytokines have been shown to upregulate secretion of the antioxidant enzyme extracellular superoxide dismutase (EC-SOD) in dermal fibroblasts and, in other cells, to stimulate production of nitric oxide (⋅ NO). Because superoxide rapidly scavenges ⋅ NO, forming the injurious peroxynitrite anion (OONO−), we hypothesize that stimulated cells upregulate EC-SOD expression concurrently with ⋅ NO release. To test for coregulation of EC-SOD and ⋅ NO within the same cell, the timing of inducible nitric oxide synthase (iNOS) and EC-SOD transcription was measured after exposure of a rat type II pneumocyte analog, the L2 cell line, to a combination of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Upregulation of iNOS and EC-SOD transcription occurred after 6 h of exposure, and transcription of both genes was linked by activation of the transcription factor nuclear factor-κB. Both EC-SOD and iNOS were elevated in rat lung homogenates 24 h after intratracheal instillation with IFN-γ and TNF-α. The observation that EC-SOD and iNOS are temporally coregulated after cytokine exposure suggests the possibility of a critical mechanism by which cells might protect ⋅ NO and avoid the formation of OONO−during inflammation.

scholarly journals Both Inducible Nitric Oxide Synthase and NADPH Oxidase Contribute to the Control of Virulent Phase I Coxiella burnetii Infections

2004 ◽  
Vol 72 (11) ◽  
pp. 6666-6675 ◽  
Author(s):  
Robert E. Brennan ◽  
Kasi Russell ◽  
Guoquan Zhang ◽  
James E. Samuel
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cell Lines ◽  
Inducible Nitric Oxide Synthase ◽  
Coxiella Burnetii ◽  
Wild Type ◽  
Primary Mouse ◽  
Ifn Γ ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Host control of Coxiella burnetii infections is believed to be mediated primarily by activated monocytes/macrophages. The activation of macrophages by cytokines leads to the production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) that have potent antimicrobial activities. The contributions of ROI and RNI to the inhibition of C. burnetii replication were examined in vitro by the use of murine macrophage-like cell lines and primary mouse macrophages. A gamma interferon (IFN-γ) treatment of infected cell lines and primary macrophages resulted in an increased production of nitric oxide (NO) and hydrogen peroxide (H2O2) and a significant inhibition of C. burnetii replication. The inhibition of replication was reversed in the murine cell line J774.16 upon the addition of either the inducible nitric oxide synthase (iNOS) inhibitor NG-monomethyl-l-arginine (NGMMLA) or the H2O2 scavenger catalase. IFN-γ-treated primary macrophages from iNOS−/− and p47phox−/− mice significantly inhibited replication but were less efficient at controlling infection than IFN-γ-treated wild-type macrophages. To investigate the contributions of ROI and RNI to resistance to infection, we performed in vivo studies, using C57BL/6 wild-type mice and knockout mice lacking iNOS or p47phox. Both iNOS−/− and p47phox−/− mice were attenuated in the ability to control C. burnetii infection compared to wild-type mice. Together, these results strongly support a role for both RNI and ROI in the host control of C. burnetii infection.

Prostasin attenuates inducible nitric oxide synthase expression in lipopolysaccharide-induced urinary bladder inflammation

2006 ◽  
Vol 291 (3) ◽  
pp. F567-F577 ◽  
Author(s):  
Li-Mei Chen ◽  
Cindy Wang ◽  
Mengqian Chen ◽  
Matthew R. Marcello ◽  
Julie Chao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mrna Expression ◽  
Inducible Nitric Oxide Synthase ◽  
Cytokine Signaling ◽  
Bladder Inflammation ◽  
Tnf Α ◽  
Cox 2 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Prostasin is a glycosylphosphatidylinositol-anchored serine protease, with epithelial sodium channel activation and tumor invasion suppression activities. We identified the bladder as an expression site of prostasin. In the mouse, prostasin mRNA expression was detected by reverse transcription and real-time polymerase chain reaction in the bladder, and the prostasin protein was localized by immunohistochemistry in the urothelial cells. In mice injected intraperitoneally with bacterial lipopolysaccharide (LPS), bladder prostasin mRNA expression was downregulated, whereas the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interferon-γ (IFN-γ), TNF-α, IL-1β, and IL-6 was upregulated. Viral promoter-driven expression of the human prostasin homolog in the bladder of transgenic mice attenuated the LPS induction of iNOS but did not abolish the induction. LPS induction of COX-2, TNF-α, IL-1β, and IL-6 expression, however, was not reduced by prostasin transgene expression. Liposome-mediated delivery of prostasin-expressing plasmid into mouse bladder produced similar attenuation effects on LPS-induced iNOS expression, while not affecting COX-2 or cytokine induction. Mice receiving plasmid expressing a catalytic mutant prostasin did not manifest the iNOS induction attenuation phenotype. We propose a proteolytic mechanism for prostasin to intercept cytokine signaling during LPS-induced bladder inflammation.

scholarly journals αβ T Cell Receptor-positive Cells and Interferon-γ, but not Inducible Nitric Oxide Synthase, Are Critical for Granuloma Necrosis in a Mouse Model of Mycobacteria-induced Pulmonary Immunopathology

2001 ◽  
Vol 194 (12) ◽  
pp. 1847-1859 ◽  
Author(s):  
Stefan Ehlers ◽  
Jochen Benini ◽  
Heinz-Dieter Held ◽  
Christiane Roeck ◽  
Gottfried Alber ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cell ◽  
Nitric Oxide Synthase ◽  
T Cell Receptor ◽  
Inducible Nitric Oxide Synthase ◽  
Bacterial Load ◽  
Cell Receptor ◽  
Ifn Γ ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The immunological basis of tuberculin-induced necrosis, known for more than a century as “Koch's phenomenon,” remains poorly understood. Aerosol infection in mice with the highly virulent Mycobacterium avium strain TMC724 causes progressive pulmonary pathology strongly resembling caseating necrosis in human patients with tuberculosis. To identify the cellular and molecular mediators causing this pathology, we infected C57BL/6 mice and mice selectively deficient in recombinase activating gene (RAG)-1, αβ T cell receptor (TCR), γδ TCR, CD4, CD8, β2-microglobulin, interferon (IFN)-γ, interleukin (IL)-10, IL-12p35, IL-12p35/p40, or iNOS with M. avium by aerosol and compared bacterial multiplication, histopathology, and respiratory physiology in these mice. The bacterial load in the lung was similarly high in all mouse groups. Pulmonary compliance, as a surrogate marker for granulomatous infiltrations in the lung, deteriorated to a similar extent in all groups of mice, except in αβ TCR-knockout (KO) and IL-12–KO mice in which compliance was higher, and in IFN-γ and inducible nitric oxide synthase–KO mice in which compliance was reduced faster. Progressive caseation of pulmonary granulomas never occurred in αβ TCR-KO, IL-12–KO, and IFN-γ–KO mice and was reduced in CD4-KO mice. In summary, αβ TCR+ cells and IFN-γ are essential for the development of mycobacteria-induced pulmonary caseous necrosis. In contrast, high mycobacterial load and extensive granulomatous infiltration per se are not sufficient to cause caseation, nor is granuloma necrosis linked to the induction of nitric oxide.

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