BACKGROUND Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases. Little is known about its role in inflammatory heart disease. METHODS AND RESULTS We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myoc...

In the present studies, the influence of inducible nitric oxide synthase (NOS) inhibition with aminoguanidine on renal function and blood pressure was examined in rats. Intravenous aminoguanidine infusion (60 mg x kg-1 x hr-1) for 40 minutes to anesthetized Sprague-Dawley rats (n=7) resulted in no significant changes in mean arterial pressure or renal cortical blood flow, while medullary blood ...

Nitric oxide synthase (NOS), the enzyme that catalyzes the formation of nitric oxide from L-arginine, exists in three major isoforms, neuronal, endothelial, and immunologic. Neuronal and endothelial isoforms are constitutively expressed, and require calcium for activation. Both of these isoforms can be induced (i.e., new protein synthesis occurs) under appropriate conditions. The immunologic is...

The innate host response to virus infection is largely dominated by the production of type I interferon and interferon stimulated genes. In particular, fibroblasts respond robustly to viral infection and to recognition of viral signatures such as dsRNA with the rapid production of type I interferon; subsequently, fibroblasts are a key cell type in antiviral protection. We recently found, howeve...

In this issue of the Journal, Gallo et al. (1) report an interesting analysis of nitric oxide production and angiogenesis in head and neck cancers. They observed the following: 1) Tumor levels of total nitric oxide synthase activity (including inducible nitric oxide synthase activity) and of 38,58 cyclic guanosine monophosphate (cGMP) (a known mediator of cellular response to nitric oxide) were...

The established dogma regarding the different isoforms of nitric oxide has been that constitutively expressed nitric oxide synthase is an extremely important homeostatic regulator of numerous important physiological processes whereas the inducible form of nitric oxide synthase underlies injury associated with intestinal inflammation. In this brief overview, I review some of the literature that ...

An in vitro model of human CMV infection of primary retinal pigment epithelial (RPE) cells was used to study the effects of cytokines on CMV replication in these cells, which are targets of CMV infection in vivo. IFN-gamma and IFN-beta were potent inhibitors of CMV replication in RPE cells, while TNF-alpha, IL-1beta, or TGF-beta2 did not affect viral replication. Inhibition by IFN-gamma, and to...

BACKGROUND In previous work, the four-amino analogue of tetrahydrobiopterin, a novel, selective inhibitor of inducible nitric oxide synthase, has been shown to prolong survival of murine cardiac allografts. METHODS To further elucidate the underlying molecular immunosuppressive mechanism, we compared the effect of four-amino tetrahydrobiopterin with that of the unsubstituted parent compound t...

Effects of nicotine on arterial endothelium-dependent relaxations mediated by nitric oxide are controversial. Experiments were designed to test the hypothesis that nicotine can directly alter activity of endothelial nitric-oxide synthase (eNOS). NOS from aortic endothelial cells of untreated dogs and recombinant eNOS, neuronal NOS, and inducible NOS were used for these experiments. NOS activity...

Studies in vitro suggested that inflammatory cytokines could cause myocardial dysfunction. However, the detailed mechanism for the cytokine-induced myocardial dysfunction in vivo remains to be examined. We thus examined this point in our new canine model in vivo, in which microspheres with and without IL-1beta were injected into the left main coronary artery. Left ventricular ejection fraction ...