scholarly journals Expression and Bactericidal Activity of Nitric Oxide Synthase in Brucella suis-Infected Murine Macrophages

1998 ◽  
Vol 66 (4) ◽  
pp. 1309-1316 ◽  
Author(s):  
Antoine Gross ◽  
Sandra Spiesser ◽  
Annie Terraza ◽  
Bruno Rouot ◽  
Emmanuelle Caron ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mouse Serum ◽  
Inos Mrna ◽  
Necrosis Factor Alpha ◽  
Murine Macrophages ◽  
Tnf Α ◽  
Brucella Suis ◽  
Ifn Γ ◽  
Oxide Synthase

ABSTRACT We examined the expression and activity of inducible nitric oxide synthase (iNOS) in both gamma interferon (IFN-γ)-treated and untreated murine macrophages infected with the gram-negative bacteriumBrucella suis. The bacteria were opsonized with a mouse serum containing specific antibrucella antibodies (ops-Brucella) or with a control nonimmune serum (c-Brucella). The involvement of the produced NO in the killing of intracellular B. suis was evaluated. B. suis survived and replicated within J774A.1 cells. Opsonization with specific antibodies increased the number of phagocytized bacteria but lowered their intramacrophage development. IFN-γ enhanced the antibrucella activity of phagocytes, with this effect being greater inops-Brucella infection. Expression of iNOS, interleukin-6, and tumor necrosis factor alpha (TNF-α) mRNAs was induced in bothc-Brucella- and ops-Brucella-infected cells and was strongly potentiated by IFN-γ. In contrast to that of cytokine mRNAs, iNOS mRNA expression was independent of opsonization. Similar levels of iNOS mRNAs were expressed in IFN-γ-treated cells infected with c-Brucella or ops-Brucella; however, expression of iNOS protein and production of NO were detected only in IFN-γ-treated cells infected with ops-Brucella. These discrepencies between iNOS mRNA and protein levels were not due to differences in TNF-α production. The iNOS inhibitorNω-nitro-l-arginine methyl ester increasedB. suis multiplication specifically in IFN-γ-treated cells infected with ops-Brucella, demonstrating a microbicidal effect of the NO produced. This observation was in agreement with in vitro experiments showing that B. suiswas sensitive to NO killing. Together our data indicate that inB. suis-infected murine macrophages, the posttranscriptional regulation of iNOS necessitates an additive signal triggered by macrophage Fcγ receptors. They also support the possibility that in mice, NO favors the elimination ofBrucella, providing that IFN-γ and antibrucella antibodies are present, i.e., following expression of acquired immunity.

scholarly journals Dexamethasone differentially affects interleukin 1β- and cyclic AMP-induced nitric oxide synthase mRNA expression in renal mesangial cells

1994 ◽  
Vol 304 (2) ◽  
pp. 337-340 ◽  
Author(s):  
D Kunz ◽  
G Walker ◽  
J Pfeilschifter
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cyclic Amp ◽  
Mesangial Cells ◽  
Inos Mrna ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Camp Analogue ◽  
Oxide Synthase ◽  
Inos Induction

Inducible nitric oxide synthase (iNOS) is expressed in renal mesangial cells in response to two principal classes of activating signals that interact in a synergistic fashion. These two groups of activators comprise inflammatory cytokines such as interleukin (IL)-1 beta or tumour necrosis factor alpha and agents that elevate cellular levels of cyclic AMP (cAMP). We examined whether dexamethasone differentially affects iNOS induction in response to IL-1 beta and a membrane-permeable cAMP analogue, N6,O-2′-dibutyryladenosine 3′,5′-phosphate (Bt2cAMP). Nanomolar concentrations of dexamethasone suppress IL-1 beta- as well as Bt2cAMP-induced iNOS protein expression and production of nitrite, the stable end product of nitric oxide (NO) formation. In contrast, dexamethasone prevents induction of iNOS mRNA in response to Bt2cAMP without affecting IL-1 beta-triggered increase in iNOS mRNA levels. These data suggest that dexamethasone acts at different levels, depending on the stimulus used to suppress iNOS induction in mesangial cells.

Antithrombin prevents endotoxin-induced hypotension by inhibiting the induction of nitric oxide synthase in rats

Blood ◽  
2002 ◽  
Vol 99 (5) ◽  
pp. 1638-1645 ◽  
Author(s):  
Hirotaka Isobe ◽  
Kenji Okajima ◽  
Mitsuhiro Uchiba ◽  
Naoaki Harada ◽  
Hiroaki Okabe
Keyword(s):  
Nitric Oxide ◽  
Septic Shock ◽  
Nitric Oxide Synthase ◽  
Messenger Rna ◽  
Inos Mrna ◽  
Therapeutic Effects ◽  
Induced Hypotension ◽  
Tnf Α ◽  
Factor Α ◽  
Oxide Synthase

Antithrombin (AT) prevents Escherichia coli–induced hypotension in animal models of sepsis, and it further reduces the mortality of patients with septic shock. In the present study, we examined whether AT may prevent the endotoxin (ET)-induced hypotension by promoting the endothelial release of prostacyclin (PGI2) in rats. Intravenous administration of AT (250 U/kg) prevented both hypotension and the increases in plasma levels of NO2−/NO3− in rats given ET. Lung expression of messenger RNA (mRNA) for tumor necrosis factor-α (TNF-α) was transiently increased after ET administration, followed by the increases in lung tissue levels of TNF-α. Both the lung activity of the inducible form of nitric oxide synthase (iNOS) and the lung expression of iNOS mRNA in animals administered ET were gradually increased after the TNF-α mRNA expression had peaked. Administration of AT significantly inhibited these increases. Neither DEGR-F.Xa, a selective inhibitor of thrombin generation, nor Trp49-modified AT, which is not capable of promoting the endothelial release of PGI2, showed any effects on these changes induced by ET. Administration of antirat TNF-α antibody produced effects similar to those induced by AT. Indomethacin pretreatment abrogated the effects induced by AT. Iloprost, a stable derivative of PGI2, produced effects similar to those of AT. These findings suggested that AT prevents the ET-induced hypotension by inhibiting the induction of iNOS through inhibiting TNF-α production. These effects of AT could be mediated by the promotion of endothelial release of PGI2 and might at least partly explain the therapeutic effects for septic shock.

scholarly journals Effect of Cytokines on Growth of Toxoplasma gondii in Murine Astrocytes

1998 ◽  
Vol 66 (10) ◽  
pp. 4989-4993 ◽  
Author(s):  
S. K. Halonen ◽  
F.-C. Chiu ◽  
L. M. Weiss
Keyword(s):  
Nitric Oxide ◽  
Central Nervous System ◽  
Nervous System ◽  
Toxoplasma Gondii ◽  
Nitric Oxide Synthase ◽  
Host Defense ◽  
Tnf Α ◽  
Important Host ◽  
Ifn Γ ◽  
Oxide Synthase

ABSTRACT Cytokines play a significant role in the regulation ofToxoplasma gondii in the central nervous system. Cytokine-activated microglia are important host defense cells in central nervous system infections. Recent evidence indicates that astrocytes can also be activated by cytokines to inhibit intracellular pathogens. In this study, we examined the effect of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-1 on the growth of T. gondii in a primary murine astrocyte culture. Pretreatment of astrocytes with IFN-γ resulted in 65% inhibition of T. gondii growth. Neither TNF-α, IL-1, nor IL-6 alone had any effect on T. gondii growth. IFN-γ in combination with either TNF-α, IL-1, or IL-6 caused a 75 to 80% inhibition of growth. While nitric oxide was produced by astrocytes treated with these cytokines, inhibition of T. gondiigrowth was not reversed by the addition of the nitric oxide synthase inhibitor N G-monomethyl-l-arginine. Furthermore, IFN-γ in combination with IL-1, IL-6, or TNF-α also induced inhibition in astrocytes derived from syngeneic mice deficient in the enzyme inducible nitric oxide synthase. This finding suggests that the mechanism of cytokine inhibition is not nitric oxide mediated. Similarly, the addition of tryptophan had no effect on inhibition, indicating that the mechanism was not mediated via induction of the enzyme indoleamine 2,3-dioxygenase. The mechanism of inhibition remains to be elucidated. Results from this study demonstrate that cytokine-activated astrocytes are capable of significantly inhibiting the growth of T. gondii. These data indicate that astrocytes may be important host defense cells in controlling toxoplasmosis in the brain.

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.

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