scholarly journals Epigenetic Silencing of the HumanNOS2Gene: Rethinking the Role of Nitric Oxide in Human Macrophage Inflammatory Responses

2014 ◽  
Vol 192 (5) ◽  
pp. 2326-2338 ◽  
Author(s):  
Thomas J. Gross ◽  
Karol Kremens ◽  
Linda S. Powers ◽  
Brandi Brink ◽  
Tina Knutson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Epigenetic Silencing ◽  
Human Macrophage

scholarly journals Toxoplasma gondii Cyclophilin 18-Mediated Production of Nitric Oxide Induces Bradyzoite Conversion in a CCR5-Dependent Manner

2009 ◽  
Vol 77 (9) ◽  
pp. 3686-3695 ◽  
Author(s):  
Hany M. Ibrahim ◽  
Hiroshi Bannai ◽  
Xuenan Xuan ◽  
Yoshifumi Nishikawa
Keyword(s):  
Nitric Oxide ◽  
Toxoplasma Gondii ◽  
Inflammatory Responses ◽  
Interleukin 12 ◽  
Dependent Manner ◽  
Independent Manner ◽  
Necrosis Factor Alpha ◽  
Parasite Multiplication ◽  
Factor Alpha

ABSTRACT Toxoplasma gondii modulates pro- and anti-inflammatory responses to regulate parasite multiplication and host survival. Pressure from the immune response causes the conversion of tachyzoites into slowly dividing bradyzoites. The regulatory mechanisms involved in this switch are poorly understood. The aim of this study was to investigate the immunomodulatory role of T. gondii cyclophilin 18 (TgCyp18) in macrophages and the consequences of the cellular responses on the conversion machinery. Recombinant TgCyp18 induced the production of nitric oxide (NO), interleukin-12 (IL-12), and tumor necrosis factor alpha through its binding with cysteine-cysteine chemokine receptor 5 (CCR5) and the production of gamma interferon and IL-6 in a CCR5-independent manner. Interestingly, the treatment of macrophages with TgCyp18 resulted in the inhibition of parasite growth and an enhancement of the conversion into bradyzoites via NO in a CCR5-dependent manner. In conclusion, T. gondii possesses sophisticated mechanisms to manipulate host cell responses in a TgCyp18-mediated process.

scholarly journals The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum

2019 ◽  
Vol 13 (11) ◽  
pp. 1057-1061
Author(s):  
Muhammad Adamu Abbas ◽  
Rapeah Suppian
Keyword(s):  
Nitric Oxide ◽  
Plasmodium Falciparum ◽  
Inflammatory Responses ◽  
Peritoneal Macrophages ◽  
Significant Inhibition ◽  
Immunomodulatory Effects ◽  
Attachment Mechanism ◽  
Significant Production ◽  
Recombinant Bcg

Introduction: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of the regulatory cytokine, IL-10, indicating significant immunomodulatory effects of the construct. The mechanism of these responses had not been established but is thought to involve toll-like receptor 4 (TLR-4). Methodology: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively. Results: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242. Conclusions: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.

scholarly journals Evaluation of Immunologic Function of Peripheral Blood Monocytes from Schizophrenic Patients in Response to Toxoplasma Gondii

2020 ◽  
pp. 1-8
Author(s):  
Ahmad Zavaran Hosseini ◽  
Ahmad Ali Noorbala ◽  
Ahmad Zavaran Hosseini ◽  
Esfandiar Azizi ◽  
Saiyad Bastaminejad ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Toxoplasma Gondii ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Inflammatory Cytokine Production ◽  
Tnf Α ◽  
Schizophrenic Patients

Background: It has been suggested that the function of myeloid immune cells, especially macrophages in schizophrenia patients (SCZ), is impaired. Considering the role of macrophages in induction of inflammatory responses, the purpose of this study is to examine the response of monocyte-derived macrophages (MDM) of schizophrenia patients to Toxoplasma gondii (T. gondii) challenge. Materials and Methods: MDMs were generated from 20 SCZ and 10 healthy controls (HC). The cells were exposed to T. gondii. The Cytokine (IL-10, IL-12, IL-6, and TNF-α) and nitric oxide (NO) productions were measured. The expression of miR146a and miR155 was examined using qPCR. Results: The level of NO was significantly higher in the supernatant of MDMs of SCZ compared with the HC (P≤0.05) in response to T. gondii. There was no difference in cytokine (IL-10, IL-12, IL-6, and TNF-α) production of SCZ compared to the controls. The effect of miR-155/ miR-146a on inflammatory cytokine production was confirmed using anti-miRNAs. There were no significant effect in miR-155/ miR-146a expression of macrophages of schizophrenia patients to T. gondii compared to control. Conclusion: In this study, although the cytokine response and the amount of miR-155/ miR-146a expression of macrophages to T. gondii was not significantly different between the schizophrenia patients and the healthy subjects, the significant differences in the production of nitric oxide strengthen the hypothesis of the functional failure of these cells.

scholarly journals Dengue Virus Infection Causes the Activation of Distinct NF-κB Pathways for Inducible Nitric Oxide Synthase and TNF-αExpression in RAW264.7 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Yi-Lin Cheng ◽  
Yee-Shin Lin ◽  
Chia-Ling Chen ◽  
Shu-Wen Wan ◽  
Yi-Dan Ou ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dengue Virus ◽  
Inflammatory Responses ◽  
Denv Infection ◽  
Raw264.7 Cells ◽  
Inflammatory Activation ◽  
Proinflammatory Responses ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Infection with dengue virus (DENV) causes an increase in proinflammatory responses, such as nitric oxide (NO) generation and TNF-αexpression; however, the molecular mechanism underlying this inflammatory activation remains undefined, although the activation of the transcription factor NF-κB is generally involved. In addition to TNF-αproduction in DENV-infected murine macrophage RAW264.7 cells, inducible NO synthase was transcriptionally and posttranslationally elevated and accompanied by NO generation. NF-κB is known to be activated by DENV infection. Pharmacologically inhibiting NF-κB activation abolishes iNOS/NO biosynthesis and TNF-αproduction. With inhibition, the potential role of NF-κB in oxidative signaling regulation was prevented during DENV infection. Heat-inactivated DENV failed to cause the identified inflammatory responses. Pharmacological inhibition of TLR3 partly decreased NF-κB activation; however, it effectively abolished inducible iNOS/NO biosynthesis but did not inhibit TNF-αproduction. In contrast to TLR3, viral protein NS2B3 also independently contributed to NF-κB activation to regulate TNF-αproduction. These results show the distinct pathways for NF-κB activation caused by DENV infection individually for the regulation of iNOS/NO and TNF-αexpression.

scholarly journals Protective role of the endothelial isoform of nitric oxide synthase in ANG II-induced inflammatory responses in the kidney

2013 ◽  
Vol 305 (7) ◽  
pp. F1031-F1041 ◽  
Author(s):  
Curtis Whiting ◽  
Alexander Castillo ◽  
Mohammed Z. Haque ◽  
Dewan S. A. Majid
Keyword(s):  
Nitric Oxide ◽  
High Mortality ◽  
Renal Injury ◽  
Inflammatory Responses ◽  
Protective Role ◽  
Ang Ii ◽  
Wild Type ◽  
Tnf Α ◽  
Oxide Synthase

In the present study, we examine the hypothesis that the nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a protective role in the development of ANG II-induced hypertension and renal injury by minimizing oxidative stress and the inflammation induced by TNF-α. Systolic blood pressure (SBP) and renal injury responses to chronic infusions of ANG II (via implanted minipumps) were evaluated for 2 wk in wild-type (WT) and in eNOS knockout mice (KO) cotreated with or without a superoxide (O2−) scavenger, tempol (400 mg/l in the drinking water), or a TNF-α receptor blocker, etanercept (5 mg/kg/day ip). In study 1, when ANG II was given at a dose of 25 ng/min, it increased mean SBP in WT mice (Δ36 ± 3 mmHg; n = 7), and this effect was attenuated in mice pretreated with tempol (Δ24 ± 3 mmHg; n = 6). In KO mice ( n = 9), this dose of ANG II resulted in severe renal injury associated with high mortality. To avoid this high mortality in KO, study 2 was conducted with a lower dose of ANG II (10 ng/min) that increased SBP slightly in WT (Δ17 ± 7 mmHg; n = 6) but exaggeratedly in KO (Δ48 ± 12 mmHg, n = 6) associated with severe renal injury. Cotreatment with either tempol ( n = 6) or etanercept ( n = 6) ameliorated the hypertensive, as well as the renal injury responses in KO compared with WT. These data demonstrate a protective role for eNOS activity in preventing renal inflammatory injury and hypertension induced by chronic increases in ANG II.

scholarly journals Differential Modulation of the Phospholipidome of Proinflammatory Human Macrophages by the Flavonoids Quercetin, Naringin and Naringenin

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3460
Author(s):  
Tiago A. Conde ◽  
Luís Mendes ◽  
Vítor M. Gaspar ◽  
João F. Mano ◽  
Tânia Melo ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Human Macrophage ◽  
Immunomodulatory Activity ◽  
Differential Modulation ◽  
Immunomodulatory Effects ◽  
Human Macrophages ◽  
Future Studies ◽  
Ifn Γ ◽  
Unique Signature

The immunomodulatory activity of flavonoids is increasingly appreciated. Macrophage phospholipids (PLs) play crucial roles in cell-mediated inflammatory responses. However, little is known on how these PLs are affected upon flavonoid treatment. In this work, we have used mass-spectrometry-based lipidomics to characterize the changes in the phospholipidome of proinflammatory human-macrophage-like cells (THP-1-derived and LPS+IFN-γ-stimulated) incubated with non-cytotoxic concentrations of three flavonoids: quercetin, naringin and naringenin. One hundred forty-seven PL species belonging to various classes were identified, and their relative abundances were determined. Each flavonoid displayed its own unique signature of induced effects. Quercetin produced the strongest impact, acting both on constitutive PLs (phosphatidylcholines, phosphatidylethanolamines and sphingomyelins) and on minor signaling lipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS) species. Conversely, naringin hardly affected structural PLs, producing changes in signaling molecules that were opposite to those seen in quercetin-treated macrophages. In turn, albeit sharing some effects with quercetin, naringenin did not change PI and PS levels and interfered with a set of phosphatidylcholines distinct from those modulated by quercetin. These results demonstrate that flavonoids bioactivity involves profound and specific remodeling of macrophage phospholipidome, paving the way to future studies on the role of cellular phospholipids in flavonoid-mediated immunomodulatory effects.

A critical role of iNOS-derived Nitric Oxide (NO) and progesterone in implantation

1998 ◽  
Vol 5 (1) ◽  
pp. 115A-115A
Author(s):  
K CHWALISZ ◽  
E WINTERHAGER ◽  
T THIENEL ◽  
R GARFIELD
Keyword(s):  
Nitric Oxide ◽  
Critical Role
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