Deficiency of Nitric Oxide Synthase 2 Results in Increased Neointima Formation in a Mouse Model of Vascular Injury

ABSTRACT The interleukin-12 and gamma interferon (IFN-γ) pathway of macrophage activation plays a pivotal role in controlling tuberculosis. In the murine model, the generation of supplementary nitric oxide by the induction of the nitric oxide synthase 2 (NOS2) gene product is considered the principal antimicrobial mechanism of IFN-γ-activated macrophages. Using a low-dose aerosol-mediated infection model in the mouse, we have investigated the role of nitric oxide in controllingMycobacterium tuberculosis in the lung. In contrast to the consequences of a systemic infection, a low dose of bacteria introduced directly into the lungs of mice lacking the NOS2 gene is controlled almost as well as in intact animals. This is in contrast to the rapid progression of disease in mice lacking IFN-γ or a key member of the IFN signaling pathway, interferon regulatory factor 1. Thus while IFN-γ is pivotal in early control of bacterial growth in the lung, this control does not completely depend upon the expression of the NOS2 gene. The absence of inducible nitric oxide in the lung does, however, result in increased polymorphonuclear cell involvement and eventual necrosis in the pulmonary granulomas of the infected mice lacking the NOS2 gene.

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Chapter 18 Expression of nitric oxide synthase-2 in glia associated with CNS pathology

Progress in Brain Research - Nitric Oxide in Brain Development, Plasticity, and Disease ◽

10.1016/s0079-6123(08)63213-6 ◽

1998 ◽

pp. 253-267 ◽

Cited By ~ 43

Author(s):

Angela K. Loihl ◽

Sean Murphy

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Cns Pathology ◽

Nitric Oxide Synthase 2 ◽

Oxide Synthase

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Requirement of nuclear factor kappaB for the constitutive expression of nitric oxide synthase-2 and cyclooxygenase-2 in rat trophoblasts

Journal of Cell Science ◽

10.1242/jcs.112.18.3147 ◽

1999 ◽

Vol 112 (18) ◽

pp. 3147-3155

Author(s):

N.A. Callejas ◽

M. Casado ◽

L. Bosca ◽

P. Martin-Sanz

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Cyclooxygenase 2 ◽

Nuclear Factor Kappab ◽

Mrna Levels ◽

Nuclear Factor ◽

Cox 2 ◽

Nf Kappab ◽

Nitric Oxide Synthase 2 ◽

Oxide Synthase

Recently isolated trophoblasts express nitric oxide synthase 2 (NOS-2) and cyclooxygenase 2 (COX-2), decreasing the levels of the corresponding mRNAs when the cells were maintained in culture. The sustained expression of COX-2 and NOS-2 in trophoblasts was dependent on the activation of nuclear factor kappaB (NF-kappaB) since proteasome inhibitors and antioxidants that abrogated NF-kappaB activity suppressed the induction of both genes. The time-dependent fall of the mRNA levels of NOS-2 and COX-2 paralleled the inhibition of NF-kappaB, determined by electrophoretic mobility shift assays, and the increase of the IkappaBalpha and IkappaBbeta inhibitory proteins. Isolated trophoblasts synthesized reactive oxygen intermediates (ROI), a process impaired after culturing the cells, and that might be involved in the NF-kappaB activation process. Moreover, treatment of recently isolated cells with ROI scavengers suppressed the expression of COX-2 and NOS-2. Challenge of trophoblasts with interleukin-1beta up-regulated the expression of both proteins, an effect that was potentiated by lipopolysaccharide. These results indicate that the physiological expression of NOS-2 and COX-2 in trophoblasts involves a sustained activation of NF-kappaB which inhibition abrogates the inducibility of both genes.

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