scholarly journals Gold Clusters Attenuate Inflammation in Rat Mesangial Cells via Inhibiting the Activation of NF-κB Pathway

Nanomaterials ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 712
Author(s):  
Jinling Yuan ◽  
Kaixiao Hou ◽  
Yawen Yao ◽  
Zhongying Du ◽  
Cao Lu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Kidney Injury ◽  
Gold Clusters ◽  
No Production ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Incidence And Mortality

Sepsis-induced acute kidney injury (AKI) with high incidence and mortality rates remains a great challenge in the clinic; thus, novel therapies need to be developed urgently. This complication is associated with an overwhelming systemic inflammatory response. The aim of this study was to evaluate the potential effects and possible mechanisms of gold clusters on septic AKI in vitro. Rat mesangial HBZY-1 cells were treated with peptide-templated gold clusters under lipopolysaccharide (LPS) stimulation. The LPS-induced expression of pro-inflammatory cytokines was measured, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6). Our data showed that the LPS-induced transcription and secretion of these cytokines were suppressed by pretreatment of gold clusters in a dose-dependent manner. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) also play key roles in septic AKI and both of them are induced upon LPS-stimulation in mesangial cells. Our results further showed that pretreatment with gold clusters dramatically inhibited the LPS-stimulated transcription and expression of COX2 and iNOS, and the subsequent prostaglandin E2 (PGE2) and nitric oxide (NO) production in HBZY-1 cells. Since these factors are involved in the NF-κB pathway upon LPS stimulation, the potential roles of gold clusters on the NF-κB pathway were further determined. We found that LPS-induced NF-κB activation was suppressed in gold clusters-pretreated HBZY-1 cells. These results demonstrated that gold clusters can attenuate LPS-induced inflammation in mesangial cells, probably via inhibiting the activation of the NF-κB pathway, suggesting a potential therapeutic approach for septic AKI.

scholarly journals Leukotriene B4 Induces Nitric Oxide Synthesis in Trypanosoma cruzi-Infected Murine Macrophages and Mediates Resistance to Infection

2002 ◽  
Vol 70 (8) ◽  
pp. 4247-4253 ◽  
Author(s):  
A. Talvani ◽  
F. S. Machado ◽  
G. C. Santana ◽  
A. Klein ◽  
L. Barcelos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Trypanosoma Cruzi ◽  
Leukotriene B4 ◽  
No Production ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT The production of nitric oxide (NO) by gamma interferon (IFN-γ)-activated macrophages is a major effector mechanism during experimental Trypanosoma cruzi infection. In addition to IFN-γ, chemoattractant molecules, such as platelet-activating factor (PAF) and CC chemokines, may also activate macrophages to induce NO and mediate the killing of T. cruzi in an NO-dependent manner. Here we investigated the ability of leukotriene B4 (LTB4) to induce the production of NO by macrophages infected with T. cruzi in vitro and whether NO mediated LTB4-induced parasite killing. The activation of T. cruzi-infected but not naive murine peritoneal macrophages with LTB4 induced the time- and concentration-dependent production of NO. In addition, low concentrations of LTB4 acted in synergy with IFN-γ to induce NO production. The NO produced mediated LTB4-induced microbicidal activity in macrophages, as demonstrated by the inhibitory effects of an inducible NO synthase inhibitor. LTB4-induced NO production and parasite killing were LTB4 receptor dependent and were partially blocked by a PAF receptor antagonist. LTB4 also induced significant tumor necrosis factor alpha (TNF-α) production, and blockade of TNF-α suppressed LTB4-induced NO release and parasite killing. A blockade of LTB4 or PAF receptors partially inhibited IFN-γ-induced NO and TNF-α production but not parasite killing. Finally, daily treatment of infected mice with CP-105,696 was accompanied by a significantly higher level of blood parasitemia, but not lethality, than that seen in vehicle-treated animals. In conclusion, our results suggest a role for LTB4 during experimental T. cruzi infection. Chemoattractant molecules such as LTB4 not only may play a major role in leukocyte migration into sites of inflammation in vivo but also, in the event of an infection, may play a relevant role in the activation of recruited leukocytes to kill the invading microorganism in an NO-dependent manner.

Determination of the enhancing action of HSP90 on neuronal nitric oxide synthase by EPR spectroscopy

2001 ◽  
Vol 281 (6) ◽  
pp. C1819-C1824 ◽  
Author(s):  
Yao Song ◽  
Jay L. Zweier ◽  
Yong Xia
Keyword(s):  
Nitric Oxide ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Heat Shock Protein 90 ◽  
Tryptophan Fluorescence ◽  
Hsp90 Inhibitor ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Dependent Manner ◽  
Intact Cells

Recent studies showed that heat shock protein 90 (HSP90) enhances nitric oxide (NO) synthesis from endothelial and neuronal NO synthase (eNOS and nNOS, respectively). However, these findings were based on indirect NO measurements. Moreover, although our previous studies showed that the action of HSP90 involves increased Ca2+/calmodulin (Ca2+/CaM) binding, quantitative measurements of the effect of HSP90 on CaM binding to nNOS have been lacking. With electron paramagnetic resonance spectroscopy, we directly measured NO signals from purified nNOS. HSP90 augmented NO formation from nNOS in a dose-dependent manner. Tryptophan fluorescence-quenching measurements revealed that HSP90 markedly reduced the K d of CaM to nNOS (0.5 ± 0.1 nM vs. 9.4 ± 1.8 nM in the presence and absence of HSP90, P < 0.01). Ca2+ ionophore triggered strong NO production from nNOS-transfected cells, and this was significantly reduced by the HSP90 inhibitor geldanamycin. Thus these studies provide direct evidence demonstrating that HSP90 enhances nNOS catalytic function in vitro and in intact cells. The effect of HSP90 is mediated by the enhancement of CaM binding to nNOS.

scholarly journals Suppression of interleukin 8 production by progesterone in rabbit uterine cervix

1994 ◽  
Vol 301 (1) ◽  
pp. 183-186 ◽  
Author(s):  
A Ito ◽  
K Imada ◽  
T Sato ◽  
T Kubo ◽  
K Matsushima ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Interleukin 1 ◽  
Interleukin 8 ◽  
Cervical Ripening ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Steady State Levels ◽  
Neutrophil Chemotactic Factor

Uterine cervical fibroblasts prepared from rabbits at 23 days of gestation were found to produce spontaneously the neutrophil chemotactic factor/interleukin 8 (IL-8). When the cells were treated with recombinant human interleukin 1 alpha and 1 beta (rhIL-1 alpha and -1 beta), both cytokines similarly enhanced the production of IL-8 in a dose-dependent manner. Recombinant tumour necrosis factor alpha also enhanced its production to a lesser extent, but interleukin 6 failed to modulate the production. Physiological concentrations of progesterone suppressed both the spontaneous and IL-1-mediated production of IL-8 in parallel with the decrease in the steady-state levels of its mRNA. These suppressive actions of progesterone were offset by co-treatment of cells with a progesterone antagonist, mifepristone (RU486). In conclusion, basal and IL-1-induced IL-8 production in rabbit uterine cervical fibroblasts is down-regulated by progesterone at the transcriptional level. These results obtained in vitro and our previous observations indicating that progesterone modulates the extra-cellular matrix breakdown via the suppression of production of matrix metalloproteinases and the augmentation of production matrix metalloproteinases and the augmentation of production of their specific inhibitors (TIMP-1) [Sato, Ito, Mori, Yamashita, Hayakawa and Nagase (1991) Biochem. J. 275, 645-650] may explain the mechanisms of the maintenance of pregnancy until parturition and the acceleration of uterine cervical ripening and dilatation at term.

scholarly journals ANTI-INFLAMMATORY ACTIVITY OF TINOCRISPOSIDE BY INHIBITING NITRIC OXIDE PRODUCTION IN LIPOPOLYSACCHARIDES-STIMULATED RAW 264.7 CELLS

2018 ◽  
Vol 11 (4) ◽  
pp. 149 ◽  
Author(s):  
Adek Zamrud Adnan ◽  
Muhammad Taher ◽  
Tika Afriani ◽  
Annisa Fauzana ◽  
Dewi Imelda Roesma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Diseases ◽  
Positive Control ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Anti Inflammatory

 Objective: The aim of this study was to investigate in vitro anti-inflammatory activity of tinocrisposide using lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophage cells. Tinocrisposide is a furano diterpene glycoside that was isolated in our previous study from Tinospora crispa.Methods: Anti-inflammatory effect was quantified spectrometrically using Griess method by measuring nitric oxide (NO) production after the addition of Griess reagent.Results: The sample concentrations of 1, 5, 25, 50, and 100 μM and 100 μM of dexamethasone (positive control) have been tested against the LPS-stimulated RAW 264.7 cells, and the results showed NO level production of 39.23, 34.00, 28.9, 20.25, 16.3, and 13.68 μM, respectively, and the inhibition level of 22.67, 33.00, 43.03, 60.10, 68.00, and 73%, respectively.Conclusions: From the study, it could be concluded that tinocrisposide was able to inhibit the formation of NO in the LPS-stimulated RAW 264.7 cells in concentration activity-dependent manner, with half-maximal inhibition concentration 46.92 μM. It can be developed as anti-inflammatory candidate drug because NO is a reactive nitrogen species which is produced by NO synthase. The production of NO has been established as a mediator in inflammatory diseases.

Activation of Nitric Oxide Release and Oxidative Metabolism by Leukotrienes B4, C4, and D4 in Human Polymorphonuclear Leukocytes

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1399-1405 ◽  
Author(s):  
Gerd Lärfars ◽  
Frédérique Lantoine ◽  
Marie-Aude Devynck ◽  
Jan Palmblad ◽  
Hans Gyllenhammar
Keyword(s):  
Nitric Oxide ◽  
Rank Order ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Kinetic Properties ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cysteinyl Leukotrienes ◽  
Mediators Of Inflammation

Abstract Because arachidonate metabolites are potent mediators of inflammation, we have studied the effects of leukotriene B4(LTB4) and the cysteinyl leukotrienes C4 and D4 (LTC4 and LTD4) on the release of nitric oxide (NO), in vitro, by human polymorphonuclear granulocytes (PMN). Two independent and highly sensitive real-time methods were used for these studies, ie, the NO-dependent oxidation of oxyhemoglobin (HbO2) to methemoglobin and a NO-sensitive microelectrode. When activated with LTB4, LTC4, or LTD4, but not with other lipoxygenase products such as 5S-HETE, 5-oxo-ETE or 5S,12S-diHETE, PMN produced NO in a stimulus- and concentration-dependent manner. The rank order of potency was LTB4 = LTC4 &gt; LTD4, corresponding to 232 ± 50 pmol of NO/106 PMN for 100 nmol/L LTB4 after 30 minutes. The kinetic properties of the responses were similar for all three leukotrienes with a maximum response at 13 ± 3 minutes. Cysteinyl leukotriene and LTB4 antagonists inhibited the agonist-induced NO production by 70%, and treatment with Bordetella pertussis toxin, or chelation of cytosolic Ca2+, [Ca2+]i, also efficiently inhibited this response. In contrast, treatment of PMN with cytochalasin B (5 μg/mL) enhanced the LTB4-induced NO formation by 86%. Thus, this is the first demonstration that the cysteinyl leukotrienes LTC4 and LTD4, as well as LTB4, activate NO release from human PMN by surface receptor, G-protein and [Ca2+]i-dependent mechanisms. This effect differs from activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, for which only LTB4is an activator.

scholarly journals Cells isolated from the human cortical interstitium resemble myofibroblasts and bind neutrophils in an ICAM-1--dependent manner.

1997 ◽  
Vol 8 (4) ◽  
pp. 604-615 ◽  
Author(s):  
A Clayton ◽  
R Steadman ◽  
J D Williams
Keyword(s):  
Smooth Muscle Actin ◽  
Interleukin 1 ◽  
Selection Marker ◽  
Specific Marker ◽  
Dependent Manner ◽  
Alpha Smooth Muscle Actin ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Inflammatory Infiltrates

Progressive renal disease is frequently accompanied by renal interstitial inflammation and fibrosis in which the activity of resident fibroblasts may be of central importance. Because there are relatively few fibroblasts in the normal cortical interstitium and there is no specific marker to permit their identification, these cells have proved difficult to characterize in vitro. In this study, these cells were isolated and established in culture, using CD90 as a positive selection marker. Antibodies to CD90 bound to tubular epithelial cells and fibroblasts, but not to glomerular cells in kidney sections. In culture, only fibroblasts were CD90-positive. These normal renal cortical fibroblasts (RCF) were alpha-smooth muscle actin- and vimentin-positive, but desmin-, cytokeratin-, and factor VIII-negative, identifying them as myofibroblasts. They expressed platelet-derived growth factor alpha and beta receptors; CD44; and alpha 2, beta 1, and beta 3 integrin chains: this combination of markers was also characteristic of fibroblasts in sections of normal cortex. These cells were positive for ICAM-1 but negative for VCAM-1. Similarly, proliferating or growth-arrested renal cortical fibroblasts (RCF) in culture expressed ICAM-1 but not VCAM-1. The expression of VCAM-1 was detected, however, and that of ICAM-1 was increased on fibroblasts associated with inflammatory infiltrates in sections from fibrotic kidneys, and ICAM-1 and VCAM-1 were up-regulated on RCF in culture after incubation with increasing doses of interleukin-1 beta or tumor necrosis factor alpha (maximum between 24 and 48 h). These adhesion molecules were functional, and neutrophils adhered to resting and cytokine-activated RCF. Binding was maximal between 24 and 48 h after cytokine treatment and was inhibited by anti-CD18 antibodies. ICAM-1 is the principal adhesion molecule controlling inflammatory cell infiltration of the interstitium. The study presented here suggests that cortical fibroblasts may be central to the control of this infiltration.

Hydrogen peroxide downregulates IL-1-driven mesangial iNOS activity: implications for glomerulonephritis

1997 ◽  
Vol 272 (6) ◽  
pp. F721-F728 ◽  
Author(s):  
E. A. Jaimes ◽  
K. A. Nath ◽  
L. Raij
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Inos Mrna ◽  
No Production ◽  
Glomerular Injury ◽  
Inos Activity ◽  
Oxide Synthase

In glomerulonephritides, autacoids such as nitric oxide (NO), reactive oxygen species, and prostanoids are produced in increased amounts in response to cytokines such as interleukin-1 (IL-1). These autacoids influence the expression of glomerular injury by their direct as well as interactive actions. We studied the effect of hydrogen peroxide (H2O2) on NO production in rat mesangial cells. We demonstrate that transient exposure of mesangial cells to H2O2 prior to sustained exposure to IL-1 decreased extracellular accumulation of NO2/NO3 and cellular guanosine 3,'5'-cyclic monophosphate (cGMP) content. H2O2 markedly impaired inducible nitric oxide synthase (iNOS) activity induced by IL-1 directly measured by the conversion of L-[14C]arginine to L-[14C]citrulline. Such impairment in iNOS activity was accompanied by a parallel reduction in iNOS protein abundance but not by a reduced expression of iNOS mRNA. The inhibitory effect of H2O2 on NOS activity was further supported by peroxide-induced impairment in IL-1-driven, NO-dependent synthesis of prostaglandin E2. Our studies thus provide the first direct evidence of a posttranscriptional inhibitory effect of H2O2 on iNOS activity. Additionally, our studies uncover the existence of a previously unrecognized effect of H2O2 on the production of NO that may exert influence on the severity of glomerular injury during glomerular inflammation.

scholarly journals Epithelial Invasion by Escherichia coli Bearing Dr Fimbriae Is Controlled by Nitric Oxide-Regulated Expression of CD55

2004 ◽  
Vol 72 (5) ◽  
pp. 2907-2914 ◽  
Author(s):  
Li Fang ◽  
Bogdan J. Nowicki ◽  
Petri Urvil ◽  
Pawel Goluszko ◽  
Stella Nowicki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Escherichia Coli ◽  
Epithelial Cell Line ◽  
No Production ◽  
Dependent Manner ◽  
E Coli ◽  
Regulated Expression ◽  
Ishikawa Cells ◽  
Epithelial Invasion

ABSTRACT We previously reported that inhibition of nitric oxide (NO) increases the rate of bacteremia and maternal mortality in pregnant rats with uterine infection by Escherichia coli expressing the Dr fimbria (Dr+). Epithelial binding and invasion by Dr+ E. coli has also been shown to be dependent upon the expression level of the cellular receptor decay-accelerating factor (DAF; CD55). Here, we hypothesize that NO-related severity of infection could be mediated by changes in DAF expression and in the rate of epithelial invasion. The cellular basis of NO effects on epithelial invasion with Dr+ E. coli was studied using Ishikawa endometrial carcinoma cells as an in vitro model of the human endometrial epithelium. Initially, we show that Ishikawa cells produce NO and express both NO synthase enzymes, NOS II and NOS III, and DAF protein. We next tested the abilities of both Dr+ E. coli and a Dr− E. coli mutant to invade Ishikawa cells, and invasion was seen only with Dr+ E. coli. Invasion by Dr+ E. coli was decreased by elevated NO production and increased by NO inhibition. Elevated NO production significantly decreased DAF protein and mRNA expression in Ishikawa cells in a time- and dose-dependent manner. Here, we propose that in vitro invasion of an epithelial cell line is directly related to NO-regulated expression of DAF. The significance of NO-regulated receptor-ligand invasion is that it may represent a novel unrecognized phenomenon of epithelial defense against infection.

Gigantol Alleviates IL-1β-Induced Inflammation and Catabolism in Mouse Osteoarthritis via PI3K/Akt/NF-κB Pathways In Vivo and In Vitro

2021 ◽  
Author(s):  
Gaosheng Zhu ◽  
Keze Miao ◽  
Mingwei Dong ◽  
Jie Cai ◽  
Zhihao Shen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Option ◽  
Interleukin 1 ◽  
Cartilage Degradation ◽  
Research Society ◽  
Necrosis Factor Alpha ◽  
Persistent Inflammation ◽  
Anti Inflammatory

Abstract Osteoarthritis (OA), a prevalent disabling disease, is characterized by irreversible cartilage degradation and persistent inflammation. The etiology as well as pathogenesis of OA are not completely unclear and need further investigation. Gigantol, is a bibenzyl derivative extracted from Dendrobium plants and has been found exhibit multiple effects such as anti-inflammatory effects. Nevertheless, the biological function of gigantol on osteoarthritis (OA) is still uncertain. This study aimed at examining the anti-inflammatory effects and latent mechanisms of gigantol in IL-1β-mediated OA progression. In vitro, we identified that gigantol treatment suppressed tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) in interleukin-1 beta (IL-1β) mediated mouse OA chondrocytes. Gigantol was also shown to dose dependently downregulate the metalloproteinase 13 (MMP13) as well as thrombospondin motifs 5 (ADAMTS5) levels. Moreover, IL-1β-mediated AKT and PI3K phosphorylation as well as NF-κB activation were inhibited by gigantol. Meanwhile, in vivo, we detected that gigantol treatment inhibited degradation of the cartilage degradation and lowered the Osteoarthritis Research Society International scores (OARSI) in OA mouse. Therefore, gigantol is a promising therapeutic option for OA.

Roles of IL-1 and TNF-alpha in endotoxin-induced activation of nitric oxide synthase in cultured rat brain cells

1996 ◽  
Vol 270 (2) ◽  
pp. R326-R332 ◽  
Author(s):  
L. I. Romero ◽  
J. B. Tatro ◽  
J. A. Field ◽  
S. Reichlin
Keyword(s):  
Nitric Oxide ◽  
Interleukin 1 ◽  
Primary Cultures ◽  
Neonatal Rat ◽  
Tnf Alpha ◽  
Brain Cells ◽  
Nitrite Accumulation ◽  
No Production ◽  
Necrosis Factor Alpha ◽  
Oxide Synthase

In astrocytes and microglia, bacterial lipopolysaccharide (LPS) stimulates production and release of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO). Although IL-1 beta and TNF-alpha are themselves capable of inducing NO synthase (NOS) in glia, the specific factors mediating LPS induction of NOS in brain have not been identified. To determine whether LPS induction of NOS in brain cells is mediated by IL-1 or TNF-alpha, acting alone or in concert, the effects of IL-1-receptor antagonist (IL-1Ra) and of TNF-soluble receptor (TNFsRp55), presented individually and in combination, on LPS-induced NOS activity were tested. In glial-enriched mixed primary cultures of neonatal rat telencephalic cells, LPS (0.1-100 ng/ml), IL-1 beta (0.01-10 nM), and TNF-alpha (0.1-100 nM) each concentration dependently stimulated accumulation of nitrite, an indicator of NO production. Induction of nitrite accumulation by LPS and by IL-1 was blocked by N omega-nitro-L-arginine methyl ester and N omega-monomethyl-L-arginine, indicating that it was mediated by NOS. TNF-alpha alone induced NO production weakly as compared with IL-1, but combined submaximal concentrations of IL-1 beta (1 nM) and TNF-alpha (10 nM) induced NOS synergistically. Furthermore, TNFsRp55 and IL-1Ra each produced a dose-dependent partial inhibition of the NO response to LPS, and the effect of TNFsRp55 was equal to or greater than that of IL-1Ra. TNFsRp55 and IL-1Ra in combination were not significantly more effective than TNF-sRp55 alone. The results indicate that LPS induction of NOS activity in brain cells is mediated in part by both IL-1 beta and TNF-alpha.

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