BACKGROUND Interferon γ (IFN-γ) increases the expression of multiple genes and responses; however, the mechanisms by which IFN-γ downmodulates cellular responses is not well understood. In this study, the repression of CCL3 and CCL4 by IFN-γ and nitric oxide synthase 2 (NOS2) in macrophages and upon Salmonella typhimurium infection of mice was investigated. METHODS Small molecule regulators a...

Nitric oxide (NO(*)), an important signaling molecule and a component of inflammatory response, is involved in tumorigenesis. However, the quantity of NO(*) and the cellular microenvironment influences the role of NO(*) in tumor development. We used a genetic strategy to test the hypothesis that an inflammatory microenvironment with an enhanced level of NO(*) accelerates spontaneous tumor devel...

Nitric oxide (NO) is an important mediator of the inflammatory response. MRL-lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce NO in parallel with the development of an autoimmune syndrome with a variety of inflammatory manifestations. In previous studies, we showed that inhibiting NO production with the nonselective nitric oxide synthase (NOS) inhibitor NG-monomet...

BACKGROUND Human heart failure (HF) usually exhibits blunted response to beta-adrenergic receptor (AR) stimulation. Here, we examined whether expression of nitric oxide synthase-2 (NOS2, or inducible NOS) contributes to this loss of inotropic reserve in human HF. METHODS AND RESULTS Failing human hearts were obtained at transplantation. Contraction and [Ca2+]i measurements were performed in i...

Inducible nitric oxide synthase (iNOS or NOS2) is expressed in malignant glioma. Previously we noted that C6 glioma cells overexpressing NOS2 displayed chemoresistance against 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and other chloroethylnitrosourea derivatives with carbamoylating action. Herein we report experimental evidence supporting the contention that this NOS2 effect is mediated, at l...

BACKGROUND It has been well accepted that glial cells in the central nervous system (CNS) produce nitric oxide (NO) through the induction of a nitric oxide synthase isoform (NOS2) only in response to various insults. Recently we described rapid astroglial, NOS2-dependent, NO production in the neocortex of healthy mice on a time scale relevant to neuronal activity. To explore a possible role for...

The pathogenesis of salt-sensitive hypertension remains poorly defined, but a role for nitric oxide (NO) has been suggested. The Dahl/Rapp salt-sensitive rat possesses a defect in NO synthesis that is overcome by supplementation with L-arginine, which increases NO and cGMP production and prevents salt-sensitive hypertension. An S714P mutation of inducible NO synthase (NOS2) was subsequently ide...

Increased nitric oxide (NO) production may contribute to the pathological changes featuring in some inflammatory diseases, but the role of NO in chronic viral hepatitis is still unknown. We compared the inducible NO synthase (NOS2) expression in the liver of patients with chronic viral hepatitis with that of both nonviral liver disease and histologically normal liver. NOS2 expression was assess...

BACKGROUND Inducible nitric oxide synthase (iNOS, or NOS2) reduces the severity of accelerated graft arteriosclerosis (AGA) in transplanted organs, although the precise mechanism is unclear. METHODS AND RESULTS We transplanted wild-type murine hearts into either wild-type or NOS2-null recipient mice; we then measured cardiac allograft survival and analyzed tissue sections by immunohistochemis...

Psoriasis is an immune-mediated systemic skin disorder with a strong genetic predisposition. The gene expression of the psoriasis susceptibility Nitric oxide synthase 2 (NOS2) specifically upregulated in psoriatic involved skin. NOS2 catalyses synthesis nitric (NO), short-lived free radical and pivotal signaling molecule both pro- anti-inflammatory properties. In this study, we have investigate...