[The synergistic effect of interferon-gamma on the induction of nitric oxide synthase by lipopolysaccharide in vascular smooth muscle]. 1995

S Hattori
Department of Endocrinology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.

Bacterial lipopolysaccharide (LPS) and other immunostimulants induce an isoform of nitric oxide synthase (iNOS) in vascular smooth muscle (VSM) which produces large quantities of nitric oxide (NO) and profound vasodilation. This process has been implicated as the cause of gram-negative septic shock. It has been demonstrated that interferon-gamma (IFN) markedly potentiates cytokine-induced NO synthesis in various cell types. However, little is known about the mechanism of this enhancing effect of IFN. The present study was undertaken to investigate the effect of IFN on LPS-induced NO synthesis and iNOS mRNA expression in VSM and the possibility of nuclear factor kB (NFkB) involvement in the effect of IFN. LPS-induced NO synthesis is markedly potentiated by IFN in VSM. Expression of iNOS mRNA in VSM costimulated with IFN and LPS was greatly increased compared to that induced by LPS alone. IFN did not alter the lifetime of iNOS mRNA. LPS stimulated translocation into the nuclei of NFkB which is believed to play an important role in the induction of iNOS, but IFN did not enhance NFkB activation by LPS. These results suggest that the enhancing effect of IFN is due to the increased transcription of the iNOS gene rather than a decreased degradation of iNOS mRNA and that the NFkB activation pathway is not involved in this effect of IFN.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008297 Male Males
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D000594 Amino Acid Oxidoreductases A class of enzymes that catalyze oxidation-reduction reactions of amino acids. Acid Oxidoreductases, Amino,Oxidoreductases, Amino Acid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB

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