Molecular mechanism of T‐cell control of Chlamydia in mice: role of nitric oxide in vivo

Immunology ◽  
1996 ◽  
Vol 88 (1) ◽  
pp. 1-5 ◽  
Author(s):  
J. U. IGIETSEME
Keyword(s):  
Nitric Oxide ◽  
T Cell ◽  
Molecular Mechanism ◽  
Cell Control

Vasculoprotective Role of Inducible Nitric Oxide Synthase at Inflammatory Coronary Lesions Induced by Chronic Treatment With Interleukin-1β in Pigs in Vivo

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3104-3111 ◽  
Author(s):  
Yoshihiro Fukumoto ◽  
Hiroaki Shimokawa ◽  
Toshiyuki Kozai ◽  
Toshiaki Kadokami ◽  
Kouichi Kuwata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Chronic Treatment ◽  
Interleukin 1Β ◽  
Coronary Lesions ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Phaseolin Attenuates Lipopolysaccharide-Induced Inflammation in RAW 264.7 Cells and Zebrafish

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 420
Author(s):  
Su-Jung Hwang ◽  
Ye-Seul Song ◽  
Hyo-Jong Lee
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Raw 264.7 Cells ◽  
Network Pharmacology ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Bioactive Constituents

Kushen (Radix Sophorae flavescentis) is used to treat ulcerative colitis, tumors, and pruritus. Recently, phaseolin, formononetin, matrine, luteolin, and quercetin, through a network pharmacology approach, were tentatively identified as five bioactive constituents responsible for the anti-inflammatory effects of S. flavescentis. However, the role of phaseolin (one of the primary components of S. flavescentis) in the direct regulation of inflammation and inflammatory processes is not well known. In this study, the beneficial role of phaseolin against inflammation was explored in lipopolysaccharide (LPS)-induced inflammation models of RAW 264.7 macrophages and zebrafish larvae. Phaseolin inhibited LPS-mediated production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), without affecting cell viability. In addition, phaseolin suppressed pro-inflammatory mediators such as cyclooxygenase 2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in a dose-dependent manner. Furthermore, phaseolin reduced matrix metalloproteinase (MMP) activity as well as macrophage adhesion in vitro and the recruitment of leukocytes in vivo by downregulating Ninjurin 1 (Ninj1), an adhesion molecule. Finally, phaseolin inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB). In view of the above, our results suggest that phaseolin could be a potential therapeutic candidate for the management of inflammation.

scholarly journals Novel Insights on the Role of Nitric Oxide in the Ovary: A Review of the Literature

2021 ◽  
Vol 18 (3) ◽  
pp. 980
Author(s):  
Maria Cristina Budani ◽  
Gian Mario Tiboni
Keyword(s):  
Nitric Oxide ◽  
In Vivo Studies ◽  
Published Data ◽  
Vitro Fertilization ◽  
Peripheral Neurons ◽  
Relevant Role ◽  
Oocyte Meiotic Maturation

Nitric oxide (NO) is formed during the oxidation of L-arginine to L-citrulline by the action of multiple isoenzymes of NO synthase (NOS): neuronal NOS (nNOS), endotelial NOS (eNOS), and inducible NOS (iNOS). NO plays a relevant role in the vascular endothelium, in central and peripheral neurons, and in immunity and inflammatory systems. In addition, several authors showed a consistent contribution of NO to different aspects of the reproductive physiology. The aim of the present review is to analyse the published data on the role of NO within the ovary. It has been demonstrated that the multiple isoenzymes of NOS are expressed and localized in the ovary of different species. More to the point, a consistent role was ascribed to NO in the processes of steroidogenesis, folliculogenesis, and oocyte meiotic maturation in in vitro and in vivo studies using animal models. Unfortunately, there are few nitric oxide data for humans; there are preliminary data on the implication of nitric oxide for oocyte/embryo quality and in-vitro fertilization/embryo transfer (IVF/ET) parameters. NO plays a remarkable role in the ovary, but more investigation is needed, in particular in the context of human ovarian physiology.

scholarly journals Systems Modeling of the Role of Interleukin-21 in the Maintenance of Effector CD4+ T Cell Responses during Chronic Helicobacter pylori Infection

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Adria Carbo ◽  
Danyvid Olivares-Villagómez ◽  
Raquel Hontecillas ◽  
Josep Bassaganya-Riera ◽  
Rupesh Chaturvedi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
T Cell ◽  
Wild Type ◽  
Content Type ◽  
Interleukin 21 ◽  
H Pylori ◽  
Deficient Mice

ABSTRACTThe development of gastritis duringHelicobacter pyloriinfection is dependent on an activated adaptive immune response orchestrated by T helper (Th) cells. However, the relative contributions of the Th1 and Th17 subsets to gastritis and control of infection are still under investigation. To investigate the role of interleukin-21 (IL-21) in the gastric mucosa duringH. pyloriinfection, we combined mathematical modeling of CD4+T cell differentiation within vivomechanistic studies. We infected IL-21-deficient and wild-type mice withH. pyloristrain SS1 and assessed colonization, gastric inflammation, cellular infiltration, and cytokine profiles. ChronicallyH. pylori-infected IL-21-deficient mice had higherH. pyloricolonization, significantly less gastritis, and reduced expression of proinflammatory cytokines and chemokines compared to these parameters in infected wild-type littermates. Thesein vivodata were used to calibrate anH. pyloriinfection-dependent, CD4+T cell-specific computational model, which then described the mechanism by which IL-21 activates the production of interferon gamma (IFN-γ) and IL-17 during chronicH. pyloriinfection. The model predicted activated expression of T-bet and RORγt and the phosphorylation of STAT3 and STAT1 and suggested a potential role of IL-21 in the modulation of IL-10. Driven by our modeling-derived predictions, we found reduced levels of CD4+splenocyte-specifictbx21androrcexpression, reduced phosphorylation of STAT1 and STAT3, and an increase in CD4+T cell-specific IL-10 expression inH. pylori-infected IL-21-deficient mice. Our results indicate that IL-21 regulates Th1 and Th17 effector responses during chronicH. pyloriinfection in a STAT1- and STAT3-dependent manner, therefore playing a major role controllingH. pyloriinfection and gastritis.IMPORTANCEHelicobacter pyloriis the dominant member of the gastric microbiota in more than 50% of the world’s population.H. pyloricolonization has been implicated in gastritis and gastric cancer, as infection withH. pyloriis the single most common risk factor for gastric cancer. Current data suggest that, in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization and chronic infection. This study uses a combined computational and experimental approach to investigate how IL-21, a proinflammatory T cell-derived cytokine, maintains the chronic proinflammatory T cell immune response driving chronic gastritis duringH. pyloriinfection. This research will also provide insight into a myriad of other infectious and immune disorders in which IL-21 is increasingly recognized to play a central role. The use of IL-21-related therapies may provide treatment options for individuals chronically colonized withH. pylorias an alternative to aggressive antibiotics.

scholarly journals Induction and role of regulatory CD4+CD25+ T cells in tolerance to the transgene product following hepatic in vivo gene transfer

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1132-1140 ◽  
Author(s):  
Ou Cao ◽  
Eric Dobrzynski ◽  
Lixin Wang ◽  
Sushrusha Nayak ◽  
Bethany Mingle ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Gene Transfer ◽  
Antibody Formation ◽  
Coagulation Factor ◽  
Gene Replacement ◽  
Factor Ix ◽  
In Vivo Gene Transfer

Abstract Gene replacement therapy is complicated by the risk of an immune response against the therapeutic transgene product, which in part is determined by the route of vector administration. Our previous studies demonstrated induction of immune tolerance to coagulation factor IX (FIX) by hepatic adeno-associated viral (AAV) gene transfer. Using a regulatory T-cell (Treg)–deficient model (Rag-2−/− mice transgenic for ovalbumin-specific T-cell receptor DO11.10), we provide first definitive evidence for induction of transgene product-specific CD4+CD25+ Tregs by in vivo gene transfer. Hepatic gene transfer–induced Tregs express FoxP3, GITR, and CTLA4, and suppress CD4+CD25− T cells. Tregs are detected as early as 2 weeks after gene transfer, and increase in frequency in thymus and secondary lymphoid organs during the following 2 months. Similarly, adoptive lymphocyte transfers from mice tolerized to human FIX by hepatic AAV gene transfer indicate induction of CD4+CD25+GITR+ that suppresses antibody formation to FIX. Moreover, in vivo depletion of CD4+CD25+ Tregs leads to antibody formation to the FIX transgene product after hepatic gene transfer, which strongly suggests that these regulatory cells are required for tolerance induction. Our study reveals a crucial role of CD4+CD25+ Tregs in preventing immune responses to the transgene product in gene transfer.

In vivo location and mechanism of EDHF-mediated vasodilation in canine coronary microcirculation

1999 ◽  
Vol 277 (3) ◽  
pp. H1252-H1259 ◽  
Author(s):  
Yasuhiro Nishikawa ◽  
David W. Stepp ◽  
William M. Chilian
Keyword(s):  
Nitric Oxide ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Direct Evidence ◽  
Coronary Microcirculation ◽  
Combined Administration ◽  
Cytochrome P 450 ◽  
Coronary Arterioles

Responses of epicardial coronary arterioles to ACh were measured using stroboscopic fluorescence microangiography in dogs ( n = 38). ACh (0.1 and 0.5 μg ⋅ kg−1 ⋅ min−1ic) dilated small (<100 μm, 11 ± 2 and 19 ± 2%, respectively) and large (>100 μm, 6 ± 3 and 13 ± 3%, respectively) arterioles at baseline. Combined administration of N ω-monomethyl-l-arginine (l-NMMA; 1.0 μmol/min ic) and indomethacin (10 mg/kg iv) eliminated ACh-induced dilation in large coronary arterioles but only partially attenuated that in small arterioles. Suffusion of a buffer containing 60 mM KCl (high KCl) completely abolished cromakalim-induced dilation in arterioles and in combination with l-NMMA plus indomethacin completely blocked ACh-induced dilation in small arterioles. This indicated that the vasodilation to ACh that persists in small arterioles after administration of l-NMMA and indomethacin is mediated via a hyperpolarizing factor. The ACh-induced vasodilation remaining after l-NMMA and indomethacin was completely blocked by the large-conductance potassium-channel antagonist iberiotoxin or by epicardial suffusion of miconazole or metyrapone, inhibitors of cytochrome P-450 enzymes. These observations are consistent with the view that endothelium-derived hyperpolarizing factor (EDHF) is a product of cytochrome P-450 enzymes and produces vasodilation by the opening of large-conductance potassium channels. We conclude that ACh-induced dilation in large coronary arterioles is mediated mainly by nitric oxide (NO), whereas, in small arterioles both NO and EDHF mediate dilation to ACh. These data provide the first direct evidence for an in vivo role of EDHF in small coronary arterioles.

scholarly journals Role of nitric oxide in hepatic microvascular injury elicited by acetaminophen in mice

2004 ◽  
Vol 286 (1) ◽  
pp. G60-G67 ◽  
Author(s):  
Yoshiya Ito ◽  
Edward R. Abril ◽  
Nancy W. Bethea ◽  
Robert S. McCuskey
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
Cell Injury ◽  
Parenchymal Cell ◽  
Protective Role ◽  
Hepatic Expression ◽  
Inos Inhibitor ◽  
Microcirculatory Disturbances

Nitric oxide (NO) is suggested to play a role in liver injury elicited by acetaminophen (APAP). Hepatic microcirculatory dysfunction also is reported to contribute to the development of the injury. As a result, the role of NO in hepatic microcirculatory alterations in response to APAP was examined in mice by in vivo microscopy. A selective inducible NO synthase (iNOS) inhibitor,l- N6-(1-iminoethyl)-lysine (l-NIL), or a nonselective NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), was intraperitoneally administered to animals 10 min before APAP gavage. l-NIL suppressed raised alanine aminotransferase (ALT) values 6 h after APAP, whereas l-NAME increased those 1.7-fold. Increased ALT levels were associated with hepatic expression of iNOS. l-NIL, but not l-NAME, reduced the expression. APAP caused a reduction (20%) in the numbers of perfused sinusoids. l-NIL restored the sinusoidal perfusion, but l-NAME was ineffective. APAP increased the area occupied by infiltrated erythrocytes into the extrasinusoidal space. l-NIL tended to minimize this infiltration, whereas l-NAME further enhanced it. APAP caused an increase (1.5-fold) in Kupffer cell phagocytic activity. This activity in response to APAP was blunted by l-NIL, whereas l-NAME further elevated it. l-NIL suppressed APAP-induced decreases in hepatic glutathione levels. These results suggest that NO derived from iNOS contributes to APAP-induced parenchymal cell injury and hepatic microcirculatory disturbances. l-NIL exerts preventive effects on the liver injury partly by inhibiting APAP bioactivation. In contrast, NO derived from constitutive isoforms of NOS exerts a protective role in liver microcirculation against APAP intoxication and thereby minimizes liver injury.

scholarly journals Nitric Oxide Overproduction by cue1 Mutants Differs on Developmental Stages and Growth Conditions

Plants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1484 ◽  
Author(s):  
Tamara Lechón ◽  
Luis Sanz ◽  
Inmaculada Sánchez-Vicente ◽  
Oscar Lorenzo
Keyword(s):  
Nitric Oxide ◽  
Carbon Metabolism ◽  
Root Elongation ◽  
Developmental Stages ◽  
Primary Root ◽  
Carbon Sources ◽  
Growth Conditions ◽  
No Production

The cue1 nitric oxide (NO) overproducer mutants are impaired in a plastid phosphoenolpyruvate/phosphate translocator, mainly expressed in Arabidopsis thaliana roots. cue1 mutants present an increased content of arginine, a precursor of NO in oxidative synthesis processes. However, the pathways of plant NO biosynthesis and signaling have not yet been fully characterized, and the role of CUE1 in these processes is not clear. Here, in an attempt to advance our knowledge regarding NO homeostasis, we performed a deep characterization of the NO production of four different cue1 alleles (cue1-1, cue1-5, cue1-6 and nox1) during seed germination, primary root elongation, and salt stress resistance. Furthermore, we analyzed the production of NO in different carbon sources to improve our understanding of the interplay between carbon metabolism and NO homeostasis. After in vivo NO imaging and spectrofluorometric quantification of the endogenous NO levels of cue1 mutants, we demonstrate that CUE1 does not directly contribute to the rapid NO synthesis during seed imbibition. Although cue1 mutants do not overproduce NO during germination and early plant development, they are able to accumulate NO after the seedling is completely established. Thus, CUE1 regulates NO homeostasis during post-germinative growth to modulate root development in response to carbon metabolism, as different sugars modify root elongation and meristem organization in cue1 mutants. Therefore, cue1 mutants are a useful tool to study the physiological effects of NO in post-germinative growth.

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