Human Immunodeficiency Virus-1–Infected Macrophages Induce Inducible Nitric Oxide Synthase and Nitric Oxide (NO) Production in Astrocytes: Astrocytic NO as a Possible Mediator of Neural Damage in Acquired Immunodeficiency Syndrome

Blood ◽  
1999 ◽  
Vol 93 (6) ◽  
pp. 1843-1850 ◽  
Author(s):  
Kotaro Hori ◽  
Parris R. Burd ◽  
Keizo Furuke ◽  
Joseph Kutza ◽  
Karis A. Weih ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Human Immunodeficiency Virus ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
No Production ◽  
Immunodeficiency Virus ◽  
Oxide Synthase ◽  
The Brain ◽  
Hiv 1 ◽  
Inducible Nitric Oxide

Nitric oxide (NO) plays an important role in normal neural cell function. Dysregulated or overexpression of NO contributes to neurologic damage associated with various pathologies, including human immunodeficiency virus (HIV)-associated neurological disease. Previous studies suggest that HIV-infected monocyte-derived macrophages (MDM) produce low levels of NO in vitro and that inducible nitric oxide synthase (iNOS) is expressed in the brain of patients with neurologic disease. However, the levels of NO could not account for the degree of neural toxicity observed. In this study, we found that induction of iNOS with concomitant production of NO occurred in primary human astrocytes, but not in MDM, when astrocytes were cocultured with HIV-1–infected MDM. This coincided with decreased HIV replication in infected MDM. Supernatants from cocultures of infected MDM and astrocytes also stimulated iNOS/NO expression in astrocytes, but cytokines known to induce iNOS expression (interferon-γ, interleukin-1β, and tumor necrosis factor-) were not detected. In addition, the recombinant HIV-1 envelope protein gp41, but not rgp120, induced iNOS in cocultures of uninfected MDM and astrocytes. This suggests that astrocytes may be an important source of NO production due to dysregulated iNOS expression and may constitute one arm of the host response resulting in suppression of HIV-1 replication in the brain. It also leads us to speculate that neurologic damage observed in HIV disease may ensue from prolonged, high level production of NO.

scholarly journals Augmented inducible nitric oxide synthase expression and increased NO production reduce sepsis-induced lung injury and mortality in myeloperoxidase-null mice

2008 ◽  
Vol 295 (1) ◽  
pp. L96-L103 ◽  
Author(s):  
Viktor Brovkovych ◽  
Xiao-Pei Gao ◽  
Evan Ong ◽  
Svitlana Brovkovych ◽  
Marie-Luise Brennan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Bacterial Colonization ◽  
Inos Expression ◽  
No Production ◽  
Bacterial Killing ◽  
E Coli ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The myeloperoxidase (MPO)-hydrogen peroxide-halide system is an efficient oxygen-dependent antimicrobial component of polymorphonuclear leukocyte (PMN)-mediated host defense. However, MPO deficiency results in few clinical consequences indicating the activation of compensatory mechanisms. Here, we determined possible mechanisms protecting the host using MPO−/−mice challenged with live gram-negative bacterium Escherichia coli. We observed that MPO−/−mice unexpectedly had improved survival compared with wild-type (WT) mice within 5–12 h after intraperitoneal E. coli challenge. Lungs of MPO−/−mice also demonstrated lower bacterial colonization and markedly attenuated increases in microvascular permeability and edema formation after E. coli challenge compared with WT. However, PMN sequestration in lungs of both groups was similar. Basal inducible nitric oxide synthase (iNOS) expression was significantly elevated in lungs and PMNs of MPO−/−mice, and NO production was increased two- to sixfold compared with WT. Nitrotyrosine levels doubled in lungs of WT mice within 1 h after E. coli challenge but did not change in MPO−/−mice. Inhibition of iNOS in MPO−/−mice significantly increased lung edema and reduced their survival after E. coli challenge, but iNOS inhibitor had the opposite effect in WT mice. Thus augmented iNOS expression and NO production in MPO−/−mice compensate for the lack of HOCl-mediated bacterial killing, and the absence of MPO-derived oxidants mitigates E. coli sepsis-induced lung inflammation and injury.

scholarly journals Cholecystokinin Inhibits Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide-Stimulated Peritoneal Macrophages

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Rafael Simone Saia ◽  
Fabíola Leslie Mestriner ◽  
Giuliana Bertozi ◽  
Fernando Queiróz Cunha ◽  
Evelin Capellari Cárnio
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Peritoneal Macrophages ◽  
Inos Expression ◽  
No Production ◽  
Camp Content ◽  
Systemic Complications ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Cholecystokinin (CCK) was first described as a gastrointestinal hormone. However, apart from its gastrointestinal effects, studies have described that CCK also plays immunoregulatory roles. Taking in account the involvement of inducible nitric oxide synthase- (iNOS-) derived NO in the sepsis context, the present study was undertaken to investigate the role of CCK on iNOS expression in LPS-activated peritoneal macrophages. Our results revealed that CCK reduces NO production and attenuates the iNOS mRNA expression and protein formation. Furthermore, CCK inhibited the nuclear factor- (NF-)κB pathway reducing IκBαdegradation and minor p65-dependent translocation to the nucleus. Moreover, CCK restored the intracellular cAMP content activating the protein kinase A (PKA) pathway, which resulted in a negative modulatory role on iNOS expression. In peritoneal macrophages, the CCK-1R expression, but not CCK-2R, was predominant and upregulated by LPS. The pharmacological studies confirmed that CCK-1R subtype is the major receptor responsible for the biological effects of CCK. These data suggest an anti-inflammatory role for the peptide CCK in modulating iNOS-derived NO synthesis, possibly controlling the macrophage activation through NF-κB, cAMP-PKA, and CCK-1R pathways. Based on these findings, CCK could be used as an adjuvant agent to modulate the inflammatory response and prevent systemic complications commonly found during sepsis.

Inducible nitric oxide synthase in the lung and exhaled nitric oxide after hyperoxia

1999 ◽  
Vol 277 (3) ◽  
pp. L636-L644 ◽  
Author(s):  
Giovanni Cucchiaro ◽  
Arthur H. Tatum ◽  
Michael C. Brown ◽  
Enrico M. Camporesi ◽  
John W. Daucher ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Septic Shock ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
Control Group ◽  
No Production ◽  
Exhaled Air ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The effect of hyperoxia on nitric oxide (NO) production in intact animals is unknown. We described the effects of hyperoxia on inducible nitric oxide synthase (iNOS) expression and NO production in the lungs of rats exposed to high concentrations of oxygen. Animals were placed in sealed Plexiglas chambers and were exposed to either 85% oxygen (hyperoxic group) or 21% oxygen (negative control group). Animals were anesthetized after 24 and 72 h of exposure and were ventilated via a tracheotomy. We measured NO production in exhaled air (ENO) by chemiluminescence. The lungs were then harvested and processed for detection of iNOS by immunohistochemistry and Western blotting analysis. The same experiments were repeated in animals exposed to hyperoxia for 72 h after they were infused with l-arginine. We used rats that were injected intraperitoneally with Escherichia coli lipopolysaccharide to induce septic shock as a positive control group. Hyperoxia and septic shock induced expression of iNOS in the lung. However, ENO was elevated only in septic shock rats but was normal in the hyperoxic group. Exogenous infusion of l-arginine after hyperoxia did not increase ENO. To exclude the possibility that in the hyperoxic group NO was scavenged by oxygen radicals to form peroxynitrite, lungs were studied by immunohistochemistry for the detection of nitrotyrosine. Nitrotyrosine was found in septic shock animals but not in the hyperoxic group, further suggesting that NO is not synthesized in rats exposed to hyperoxia. We conclude that hyperoxia induces iNOS expression in the lung without an increase in NO concentration in the exhaled air.

scholarly journals Essential amino acid tryptophan inhibits induction of inducible nitric oxide synthase gene expression in interleukin-1β stimulated hepatocytes

2019 ◽  
Vol 2 (7) ◽  
pp. 170
Author(s):  
Takumi Tsuda ◽  
Hirokazu Miki ◽  
Richi Nakatake ◽  
Tatsuma Sakaguchi ◽  
Masahiko Hatta ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
No Production ◽  
Inos Gene ◽  
Oxide Synthase ◽  
Inos Gene Expression ◽  
Inducible Nitric Oxide

Background/objective: Tryptophan exerts protective effects against a variety of organ inflammation and injury, including liver. However, there are few scientific reports about the mechanisms involved in the action. Pro-inflammatory cytokine interleukin (IL)-1β stimulates the induction of inducible nitric oxide synthase (iNOS) expression and NO production in cultured hepatocytes (“in vitro liver injury model”), and the prevention of iNOS expression and NO production is considered to be an indicator of liver protection. This study aimed to examine whether tryptophan influences the induction of iNOS gene expression and the mechanisms.Methods: Tryptophan was added into primary cultures of rat hepatocytes stimulated by IL-1β. The iNOS induction, NO production and its signaling pathway were analyzed.Results: IL-1β induced iNOS gene expression, which was followed by iNOS expression and NO production. Tryptophan inhibited the expression of iNOS mRNA and protein, and decreased the production of NO. Transfection experiments with iNOS promoter-luciferase constructs revealed that tryptophan reduced the activities of iNOS mRNA synthesis and its stability. Tryptophan blocked two essential signaling pathways, the activation of nuclear factor (NF)-κB and upregulation of type I IL-1receptor (IL-1RI).Conclusions: Results indicate that tryptophan can prevent the NO production by the inhibition of iNOS gene expression, in part through NF-κB activation and IL-1RI upregulation, in inflamed hepatocytes. Tryptophan may be a potential therapeutic treatment in injured organs, including liver.Key words: tryptophan, inducible nitric oxide synthase, nitric oxide, cultured hepatocytes, nuclear factor-κB, type I interleukin-1 receptor

scholarly journals Interleukin-1β Signals through a c-Jun N-Terminal Kinase-Dependent Inducible Nitric Oxide Synthase and Nitric Oxide Production Pathway in Sertoli Epithelial Cells

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5424-5430 ◽  
Author(s):  
Tomomoto Ishikawa ◽  
Patricia L. Morris
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
No Production ◽  
Oxygen Species ◽  
Cox 2 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Our recent Sertoli cell (SC) studies showed that the c-Jun N-terminal kinase (JNK) and inducible cyclooxygenase-2 (COX-2) pathways are key regulatory components of IL (IL-1α, IL-1β, and IL-6) expression and START-domain containing StARD1 and StARD5 proteins. IL-1β regulates SC autocrine/paracrine activities and subsequently influences developing germ cells and spermatogenesis. This study was designed to evaluate whether IL-1β mediates high-output inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in these specialized epithelial cells and characterize gonadotropin and cytokine-regulation of NO. Purified SCs were maintained in serum-free cultures and treated with FSH (100 ng–1 μg/ml) or IL-1β (10 ng/ml) in time-course studies. To determine obligatory intracellular pathways, treatments were conducted with or without activity inhibitors: COX-2 selective (NS-398, 10 μm) or JNK (SP600125, 10 μm) for 1, 3, 6, and 24 h. NOS mRNAs and proteins were evaluated by RT-PCR and Western analysis, respectively. NO and reactive oxygen species were measured by flow cytometry and ELISA. IL-1β transiently induces intracellular NO (30 min) but not reactive oxygen species. Subsequently, iNOS mRNA and protein expression (3–6 h) significantly increased after IL-1β but not FSH stimulation, and in time-dependent manner, markedly increased extracellular NO (24 h, 8-fold). No change in the constitutive endothelial NOS isoform was observed. Inhibition of JNK, but not COX-2, activity inhibits IL-1β-induced iNOS expression and NO production. Such findings suggest that intra- and extracellular NO within the tubule may alert SCs monitoring the microenvironment to an aberrant cytokine, triggering antioxidant and antiinflammatory activities to avoid disruption of spermatogenesis.

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