scholarly journals Nitric oxide production in murine spleen cells: role of interferons and prostaglandin E2in the generation of cytotoxic activity

1996 ◽  
Vol 5 (1) ◽  
pp. 62-68 ◽  
Author(s):  
Dominique Vaillier ◽  
Richard Daculsi ◽  
Norbert Gualdel
Keyword(s):  
Nitric Oxide ◽  
Cytotoxic Activity ◽  
Minor Role ◽  
No Production ◽  
Spleen Cells ◽  
Kinase C ◽  
Murine Spleen ◽  
Ifn Γ ◽  
A Minor

The production of nitric oxide (NO) was measured in cultures of spleen cells stimulated by lipopolysaccharide (LPS), IL-2 or LPS + IL-2. We observed that NO synthesis is increased by IFN-γ but inhibited by IFN-α/β. This is not the case when IL-2 is present in the cultures, since interferons play a minor role in the regulation of the NO production. When IL-2 and LPS were associated in the cultures, the IFN-α/β role seems more important than that of IFN-γ. PGE2inhibits NO production in LPS supplemented cultures but has a slight effect in the presence of IL-2 and no effect with IL-2 + LPS. 3-isoButyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterases, induces a decrease of IFN production. In the presence of H-7, an inhibitor of protein kinase C (PKC), NO production is reduced when the cultures are supplemented by LPS or IL-2 but not when IL-2 and LPS are both added. H-7 also reduced IFN production. In the presence of NG-monomethyl-L-arginine (N-MMA), an inhibitor of NO synthesis, IFN production was increased, with no change in the cytotoxic activity. Hence, interferons regulate NO production by mouse spleen cells and, in return, NO modulates the generation of IFN.

scholarly journals Induction of Gamma Interferon and Nitric Oxide by Truncated Pneumolysin That Lacks Pore-Forming Activity

2002 ◽  
Vol 70 (1) ◽  
pp. 107-113 ◽  
Author(s):  
Hisashi Baba ◽  
Ikuo Kawamura ◽  
Chikara Kohda ◽  
Takamasa Nomura ◽  
Yutaka Ito ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Neutralizing Antibody ◽  
Cytolytic Activity ◽  
Gamma Interferon ◽  
Full Length ◽  
No Production ◽  
Spleen Cells ◽  
Ifn Γ ◽  
Oxide Synthase

ABSTRACT Pneumolysin (PLY), an important virulence factor of Streptococcus pneumoniae, is known to exert various effects on the host immune cells, including cytokine induction, in addition to its known cytolytic activity as a member of the thiol-activated cytolysins. It is of interest to determine whether cytolytic activity is involved in triggering the cytokine production. In this study, we constructed full-length recombinant PLY and noncytolytic truncated PLYs with C-terminal deletions to examine the response of spleen cells to these PLY preparations. When cytolytic activity was blocked by treatment with cholesterol, full-length PLY was capable of inducing gamma interferon (IFN-γ) production. Truncated PLYs that originally exhibited no cytolytic activity were also active in IFN-γ induction. Therefore, the IFN-γ-inducing ability of PLY appeared to be independent of the cytolytic activity. Furthermore, IFN-γ-inducing preparations were also capable of inducing nitric oxide synthase expression and nitric oxide (NO) production, and the addition of neutralizing antibody to IFN-γ abolished the NO production. These results clearly demonstrated that PLY is capable of inducing IFN-γ production in spleen cells by a mechanism different from pore formation and that the induced IFN-γ stimulates NO production. These findings were discussed with reference to the contribution of PLY to the virulence of S. pneumoniae in vivo.

scholarly journals Protective Role of Nitric Oxide inStaphylococcus aureus Infection in Mice

1998 ◽  
Vol 66 (3) ◽  
pp. 1017-1022 ◽  
Author(s):  
Sanae Sasaki ◽  
Tomisato Miura ◽  
Shinsuke Nishikawa ◽  
Kyogo Yamada ◽  
Mayuko Hirasue ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spleen Cell ◽  
Cell Cultures ◽  
Protective Role ◽  
Inos Mrna ◽  
No Production ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT This study was carried out to determine the role of nitric oxide (NO) in Staphylococcus aureus infection in mice. NO production in spleen cell cultures was induced by heat-killed S. aureus. Expression of mRNA of the inducible isoform of NO synthase (iNOS) was induced in the spleens and kidneys of S. aureus-infected mice. When mice were treated with monoclonal antibodies (MAbs) against tumor necrosis factor alpha (TNF-α) or gamma interferon (IFN-γ) before S. aureus infection, the induction of iNOS mRNA expression in the kidneys was inhibited. These MAbs also inhibited NO production in spleen cell cultures stimulated with heat-killed S. aureus. NO production in the spleen cell cultures and levels of urinary nitrate plus nitrite were suppressed by treatment with aminoguanidine (AG), a selective inhibitor of iNOS. The survival rates of AG-treated mice were significantly decreased by either lethal or sublethal S. aureusinfections. However, an effect of AG administration on bacterial growth was not observed in the spleens and kidneys of mice during either type of infection. Production of TNF-α and IFN-γ was not affected by AG treatment in vitro and in vivo. These results suggest that NO plays an important role in protection from lethality by the infection, but the protective role of NO in host resistance against S. aureusinfection was not proved. Moreover, our results show that TNF-α and IFN-γ regulate NO production while NO may not be involved in the regulation of the production of these cytokines during S. aureus infection.

scholarly journals Central Role of Endogenous Gamma Interferon in Protective Immunity against Blood-Stage Plasmodium chabaudi AS Infection

2000 ◽  
Vol 68 (8) ◽  
pp. 4399-4406 ◽  
Author(s):  
Zhong Su ◽  
Mary M. Stevenson
Keyword(s):  
Protective Immunity ◽  
Gamma Interferon ◽  
Blood Stage ◽  
No Production ◽  
Plasmodium Chabaudi ◽  
Spleen Cells ◽  
Parasite Antigen ◽  
Ifn Γ

ABSTRACT The role of endogenous gamma interferon (IFN-γ) in protective immunity against blood-stage Plasmodium chabaudi AS malaria was studied using IFN-γ gene knockout (GKO) and wild-type (WT) C57BL/6 mice. Following infection with 106 parasitized erythrocytes, GKO mice developed significantly higher parasitemia during acute infection than WT mice and had severe mortality. In infected GKO mice, production of interleukin 12 (IL-12) p70 and tumor necrosis factor alpha in vivo and IL-12 p70 in vitro by splenic macrophages was significantly reduced compared to that in WT mice and the enhanced nitric oxide (NO) production observed in infected WT mice was completely absent. WT and GKO mice had comparable numbers of total nucleated spleen cells and B220+ and Mac-1+spleen cells both before and after infection. Infected WT mice, however, had significantly more F4/80+, NK1.1+, and F4/80+Ia+ spleen cells than infected GKO mice; male WT had more CD3+ cells than male GKO mice. In comparison with those from WT mice, splenocytes from infected GKO mice had significantly higher proliferation in vitro in response to parasite antigen or concanavalin A stimulation and produced significantly higher levels of IL-10 in response to parasite antigen. Infected WT mice produced more parasite-specific immunoglobulin M (IgM), IgG2a, and IgG3 and less IgG1 than GKO mice. Significant gender differences in both GKO and WT mice in peak parasitemia levels, mortality, phenotypes of spleen cells, and proliferation of and cytokine production by splenocytes in vitro were apparent during infection. These results thus provide unequivocal evidence for the central role of endogenous IFN-γ in the development of protective immunity against blood-stage P. chabaudi AS.

scholarly journals Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-γ in rat

2010 ◽  
Vol 298 (6) ◽  
pp. G916-G926 ◽  
Author(s):  
Junta Ito ◽  
Hiroyuki Uchida ◽  
Takayuki Yokote ◽  
Kazuo Ohtake ◽  
Jun Kobayashi
Keyword(s):  
Nitric Oxide ◽  
Protein Expression ◽  
Interferon Γ ◽  
No Synthase ◽  
Histological Evaluation ◽  
No Production ◽  
Ros Production ◽  
Nitrite Production ◽  
Ifn Γ

Nitric oxide (NO) is associated with intestinal apoptosis in health and disease. This study aimed to investigate the role of intestinal NO in the regulation of apoptosis during fasting in rats. Male Wistar rats were divided into two groups and subcutaneously injected with saline (SA) or aminoguanidine (AG), followed by fasting for 24, 48, 60, and 72 h. At each time point, the jejunum was subjected to histological evaluation for enterocyte apoptosis by histomorphometric assessment and TUNEL analysis. We performed immunohistochemistry for inducible NO synthase (iNOS) expression in the jejunum and measured tissue nitrite levels using HPLC and 8-hydroxydeoxyguanosine adduct using ELISA, indicative of endogenous NO production and reactive oxygen species (ROS) production, respectively. Jejunal transcriptional levels of iNOS, neuronal NO synthase (nNOS), and interferon-γ (IFN-γ) were also determined by RT-PCR. Fasting caused significant jejunal mucosal atrophy due to attenuated cell proliferation and enhanced apoptosis with increase in iNOS transcription, its protein expression in intestinal epithelial cells (IEC), and jejunal nitrite levels. However, AG treatment histologically reduced apoptosis with inhibition of fasting-induced iNOS transcription, protein expression, and nitrite production. We also observed fasting-induced ROS production and subsequent IFN-γ transcription, which were all inhibited by AG treatment. Furthermore, we observed reduced transcriptional levels of nNOS, known to suppress iNOS activation physiologically. These results suggest that fasting-induced iNOS activation in IEC may induce apoptosis mediators such as IFN-γ via a ROS-mediated mechanism and also a possible role of nNOS in the regulation of iNOS activity in fasting-induced apoptosis.

scholarly journals Role of cytokines and nitric oxide in the induction of tuberculostatic macrophage functions

2000 ◽  
Vol 9 (6) ◽  
pp. 261-269 ◽  
Author(s):  
Vera L. Petricevich ◽  
Rosely C. B. Alves
Keyword(s):  
Nitric Oxide ◽  
Culture Media ◽  
Peritoneal Macrophages ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
No Production ◽  
Phenotypic Differences ◽  
Ifn Γ ◽  
Necrosis Factor

The aim of this study was to determine phenotypic differences when BCG invades macrophages. Bacilli prepared from the same BCG primary seed, but produced in different culture media, were analysed with respect to the ability to stimulate macrophages and the susceptibility to treatment with cytokines and nitric oxide (NO). Tumour necrosis factor (TNF) activity was assayed by measuring its cytotoxic activity on L-929 cells, interleukin-6 (IL-6) and interferon γ (IFN-γ) were assayed by enzyme-linked immunosorbent assay (ELISA), whereas NO levels were detected by Griess colorimetric reactions in the culture supernatant of macrophages incubated with IFN-γ , TNF or NO and subsequently exposed to either BCG-I or BCG-S. We found that BCG-I and BCGS bacilli showed different ability to simulate peritoneal macrophages. Similar levels of IL-6 were detected in stimulated macrophages with lysate from two BCG samples. The highest levels of TNF and IFN-γ were observed in macrophages treated with BCG-S and BCG-I, respectively. The highest levels of NO were observed in cultures stimulated for 48h with BCG-S. We also found a different susceptibility of the bacilli to ex ogenous treatm ent w ith IFN-γ and TNF which were capable of killing 60 and 70% of both bacilli, whereas NO was capable of killing about 98 and 47% of BCG-I and BCG-S, respectively. The amount of bacilli proportionally decreased with IFN-γ and TNF, suggesting a cytokine-related cytotox ic effect. Moreover, NO also decreased the viable number of bacilli. Interestingly, NO levels of peritoneal macrophages were significantly increased after cytokine treatment. This indicates that the treatment of macrophages with cytokines markedly reduced bacilli number and presented effects on NO production. The results obtained here emphasize the importance of adequate stimulation for guaranteeing efficient killing of bacilli. In this particular case, the IFN-γ and TNF were involved in the activation of macrophage bactericidal activity.

scholarly journals Hepatitis C Virus E1 Protein Enhances Macrophage iNOS Expression In Vitro

2021 ◽  
Author(s):  
Batkhishig Munkhjargal ◽  
Bilguun Enkhtuvshin ◽  
Uranbileg Ulziisaikhan ◽  
Baljinnyam Tuvdenjamts ◽  
Khulan Unurbuyan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Response ◽  
Inos Expression ◽  
No Production ◽  
E1 Protein ◽  
Ifn Γ

AbstractObjectiveHepatitis C virus (HCV) is a single-stranded RNA virus that causes chronic hepatitis, cirrhosis, and liver cancer. Approximately 170 million individuals are infected with HCV worldwide. The pathogenesis of HCV-associated liver injury is thought to be due to the host antiviral immune response, including the T cell response, and excessive production of proinflammatory cytokines, reactive oxygen species, and nitric oxide (NO).Interferon-γ (IFN-γ) is a key cytokine in the adaptive immune response that is primarily secreted from CD4+ T helper cells to induce cytotoxic T lymphocyte (CTL) cell response against HCV infection. Another important role of IFN-γ is the activation of macrophages in the liver resulting in inhibition of viral replication and increased NO production.Enhanced inducible nitric oxide synthase (iNOS) expression and NO production observed in the liver of HCV-infected patients is positively correlated with viral load and hepatic inflammation. HCV-infected macrophages are major producers of NO in the liver. It is not completely understood how HCV proteins affect iNOS expression and what the role of IFN-γ is in HCV protein expression in HCV-infected macrophages. In this study, we examined the effect of INF-γ and HCV proteins on iNOS expression in the Raw264.7 cell line.ResultsConsistent with other studies, HCV core and NS5A proteins induced iNOS expression in macrophages. Moreover, HCV E1 protein-enhanced iNOS expression is highest in the presence and absence of IFN-γ activation.ConclusionThese results indicate that hepatitis C virus core, NS5A, E1 protein regulates iNOS protein expression in IFN-γ-activated and resting macrophage cell lines. These findings points to a future research direction for understanding the pathogenesis of HCV-related liver inflammation.

scholarly journals Protective Role of Nitric Oxide in a Model of Thrombotic Microangiopathy in Rats

2001 ◽  
Vol 12 (10) ◽  
pp. 2088-2097
Author(s):  
JING SHAO ◽  
TOSHIO MIYATA ◽  
KOEI YAMADA ◽  
NORIO HANAFUSA ◽  
TAKEHIKO WADA ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Thrombotic Microangiopathy ◽  
Periodic Acid ◽  
Minor Role ◽  
Protective Mechanism ◽  
No Production ◽  
Nos Inhibitor ◽  
Inducible Nos

Abstract. A new model of thrombotic microangiopathy (TMA) was previously developed, and it was demonstrated that endothelial nitric oxide (NO) synthase (NOS) is upregulated in glomeruli in this model. It was hypothesized that the synthesis of NO, a potent vasodilator and platelet inhibitory factor, is induced as a defense mechanism. The goal of this study was to clarify the role of NO in this model.Ex vivoexperiments using Western blotting and functional assays demonstrated upregulation of endothelial NOS in isolated glomeruli from TMA rats. Inin vivoexperiments, five groups of rats were studied, including rats with TMA treated with vehicle,NG-nitro-L-arginine methyl ester (L-NAME) (a NOS inhibitor), or L-N6-(1-iminoethyl)lysine (L-NIL) (a specific inducible NOS inhibitor) and normal control rats treated with vehicle or L-NAME. Blood urea nitrogen levels, BP, urinary nitrate/nitrite excretion, and proteinuria were measured. Histologic assessments using periodic acid-Schiff staining and immunohistologic studies with markers for endothelium, platelets, fibrin, cell proliferation, and apoptosis were also performed. L-NAME inhibition of NO synthesis in rats with TMA resulted in more severe glomerular and tubulointerstitial injury, which was accompanied by thrombus formation and a marked loss of endothelial cells, with more apoptotic cells. These changes were associated with severe renal function deterioration. In contrast, these features were less pronounced in the vehicle- or L-NIL-treated rats with TMA and were absent in the control animals. In conclusion, inhibition of NO production in this model of TMA markedly exacerbated renal injury. The absence of effects with L-NIL treatment suggests a minor role for inducible NOS in this model. These results suggest that production of NO, most likely by endothelial cells, is an important protective mechanism in TMA.

The Effect of Path Length and Display Size on Memory for Spatial Information

2012 ◽  
Vol 59 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Katherine Guérard ◽  
Sébastien Tremblay
Keyword(s):  
Path Length ◽  
Potential Role ◽  
Spatial Information ◽  
Recall Performance ◽  
Minor Role ◽  
Length Effect ◽  
Serial Memory ◽  
Fixed Reference ◽  
A Minor

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

2018 ◽  
Vol 16 (2) ◽  
pp. 194-199
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Ewa Jablonska
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Polymorphonuclear Neutrophils ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
No Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

Effects of Myo-inositol Alone and in Combination with Seleno-Lmethionine on Cadmium-Induced Testicular Damage in Mice

2019 ◽  
Vol 12 (4) ◽  
pp. 311-323 ◽  
Author(s):  
Salvatore Benvenga ◽  
Antonio Micali ◽  
Giovanni Pallio ◽  
Roberto Vita ◽  
Consuelo Malta ◽  
...  
Keyword(s):  
Structural Changes ◽  
Natural Antioxidants ◽  
Minor Role ◽  
Positive Role ◽  
Testosterone Levels ◽  
Tnf Α ◽  
Testicular Lesions ◽  
A Minor ◽  
Immunohistochemical Analyses

Background: Cadmium (Cd) impairs gametogenesis and damages the blood-testis barrier. Objective: As the primary mechanism of Cd-induced damage is oxidative stress, the effects of two natural antioxidants, myo-inositol (MI) and seleno-L-methionine (Se), were evaluated in mice testes. Methods: Eighty-four male C57 BL/6J mice were divided into twelve groups: 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); Se (0.2 mg/kg/day per os); Se (0.4 mg/kg/day per os); MI (360 mg/kg/day per os); MI plus Se (0.2 mg/kg/day); MI plus Se (0.4 mg/kg/day); CdCl2 (2 mg/kg/day i.p.) plus vehicle; CdCl2 plus MI; CdCl2 plus Se (0.2 mg/kg/day); CdCl2 plus Se (0.4 mg/kg/day); CdCl2 plus MI plus Se (0.2 mg/kg/day); and CdCl2 plus MI plus Se (0.4 mg/kg/day). After 14 days, testes were processed for biochemical, structural and immunohistochemical analyses. Results: CdCl2 increased iNOS and TNF-α expression and Malondialdehyde (MDA) levels, lowered glutathione (GSH) and testosterone, induced testicular lesions, and almost eliminated claudin-11 immunoreactivity. Se administration at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression, maintained GSH, MDA and testosterone levels, structural changes and low claudin-11 immunoreactivity. MI alone or associated with Se at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression and MDA levels, increased GSH and testosterone levels, ameliorated structural organization and increased claudin-11 patches number. Conclusion: We demonstrated a protective effect of MI, a minor role of Se and an evident positive role of the association between MI and Se on Cd-induced damages of the testis. MI alone or associated with Se might protect testes in subjects exposed to toxicants, at least to those with behavior similar to Cd.

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