Inducible Nitric Oxide Synthase (iNOS) and Nitric Oxide (NO) are Important Mediators of Reflux-induced Cell Signalling in Esophageal Cells

McAdam, Elizabeth; Haboubi, Hasan; Forrester, George; Eltahir, Zakaria; Spencer-Harty, Sam; Davies, Christopher; Griffiths, Ann; Baxter, J. N.; Jenkins, Gareth

doi:10.1093/carcin/bgs241

Cited by 51 publications

(48 citation statements)

References 44 publications

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“…The activation of NF-κB mediated transcription of a number of COX-2 [45], iNOS [46], and TNF-α [47]. On the other hand, TNF-α induces activation of NF-κB in the COX-2 promoter, followed by initiation of COX-2 expression [48].…”

Section: Discussionmentioning

confidence: 99%

Toxicological Effect of Manganese on NF-κB/iNOS-COX-2 Signaling Pathway in Chicken Testes

Zhu

Teng³

et al. 2015

Biol Trace Elem Res

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Manganese (Mn) pollution can cause tissue and organ dysfunction and structural damage. The toxicity of Mn in poultry was reported, but inflammatory damage that Mn induced in the testicular tissue has not been reported. The aim of this study was to investigate the effect of Mn poisoning on NF-κB/iNOS-COX-2 signaling pathway in chicken testes. One hundred eighty Hyline male chickens at 7 days of age were fed either commercial diet or MnCl2-added commercial diet containing 600, 900, and 1800 mg/kg Mn for 30, 60, and 90 days, respectively. The messenger RNA (mRNA) expression of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), nitric oxide (NO) content, iNOS activity, and histopathology were examined in chicken testes. The results showed that excess Mn upregulated mRNA expression of NF-κB, COX-2, TNF-α, and iNOS, NO content, and iNOS activity at 60th and 90th day. Mn had a time-dependent effect on NF-κB and TNF-α mRNA expression. Mn had a dose- and time-dependent effect on NO content and iNOS activity. Mn exposure induced chicken testis histological changes in dose- and time-dependent manner. It indicated that Mn exposure resulted in inflammatory injury of chicken testis tissue through NF-κB/iNOS-COX-2 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Toxicological Effect of Manganese on NF-κB/iNOS-COX-2 Signaling Pathway in Chicken Testes

Zhu

Teng³

et al. 2015

Biol Trace Elem Res

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“…However, at the BT, peroxynitrite levels did not change under aneurysm-inducing flow conditions. An alternative candidate is NF-κB, a transcriptional regulator of MMPs that is found in SMCs of hemodynamically induced IAs [12] and which is activated by both NO [32] and superoxide [33]. Further studies are required to determine whether NO and superoxide affect SMCs via a common mediator or through independent signaling mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Nitric Oxide Synthase and Superoxide Mediate Hemodynamic Initiation of Intracranial Aneurysms

et al. 2014

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BackgroundHemodynamic insults at arterial bifurcations are believed to play a critical role in initiating intracranial aneurysms. Recent studies in a rabbit model indicate that aneurysmal damage initiates under specific wall shear stress conditions when smooth muscle cells (SMCs) become pro-inflammatory and produce matrix metalloproteinases (MMPs). The mechanisms leading to SMC activation and MMP production during hemodynamic aneurysm initiation are unknown. The goal is to determine if nitric oxide and/or superoxide induce SMC changes, MMP production and aneurysmal remodeling following hemodynamic insult.MethodsBilateral common carotid artery ligation was performed on rabbits (n = 19, plus 5 sham operations) to induce aneurysmal damage at the basilar terminus. Ligated animals were treated with the nitric oxide synthase (NOS) inhibitor LNAME (n = 7) or the superoxide scavenger TEMPOL (n = 5) and compared to untreated animals (n = 7). Aneurysm development was assessed histologically 5 days after ligation. Changes in NOS isoforms, peroxynitrite, reactive oxygen species (ROS), MMP-2, MMP-9, and smooth muscle α-actin were analyzed by immunohistochemistry.ResultsLNAME attenuated ligation-induced IEL loss, media thinning and bulge formation. In untreated animals, immunofluorescence showed increased endothelial NOS (eNOS) after ligation, but no change in inducible or neuronal NOS. Furthermore, during aneurysm initiation ROS increased in the media, but not the intima, and there was no change in peroxynitrite. In LNAME-treated animals, ROS production did not change. Together, this suggests that eNOS is important for aneurysm initiation but not by producing superoxide. TEMPOL treatment reduced aneurysm development, indicating that the increased medial superoxide is also necessary for aneurysm initiation. LNAME and TEMPOL treatment in ligated animals restored α-actin and decreased MMPs, suggesting that eNOS and superoxide both lead to SMC de-differentiation and MMP production.ConclusionAneurysm-inducing hemodynamics lead to increased eNOS and superoxide, which both affect SMC phenotype, increasing MMP production and aneurysmal damage.

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“…Regulation of NF-κB activation includes positive and negative feedback regulation. Positive feedback regulation occurs mainly in the extracellular domain, which is the extracellular mechanism of the amplification of inflammatory reaction [20, 21]. Negative feedback regulation can inhibit further activation of NF-κB and limit the continuous expansion of inflammatory reaction [22, 23].…”

Section: Discussionmentioning

confidence: 99%

The effect of NF-κB antisense oligonucleotide on transdifferentiation of fibroblast in lung tissue of mice injured by bleomycin

et al. 2014

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To investigate the influence of NF-κB antisense oligonucleotide on transdifferentiation of fibroblast in the pathological process of bleomycin-induced pulmonary fibrosis in mice. 6 h before molding of C57BL/6 model of pulmonary fibrosis in mice, NF-κB antisense oligonucleotide was injected from caudal vein. Then the lung tissue was collected for primary culture as well as model group and control group. Cultured cells were used for immunocytochemical staining of p65, IκB-α and α-SMA proteins as well as in situ hybridization staining of p65 and IκB-α. Then image analysis was carried out. The expressions of all the indicators were expressed as mean optical density. Compared with the control group, the expressions of p65 protein, IκB-α protein and α-SMA protein of model group were increased, as well as the expressions of p65 mRNA and IκB-α mRNA (P < 0.05). Compared with model group, the expressions of all indicators of intervention group were decreased (P < 0.05). P65 protein and p65 mRNA were positively correlated with the expression of α-SMA protein respectively. p65 protein and p65 mRNA were positively correlated with the expressions of IκB-α protein and IκB-α mRNA respectively. NF-κB antisense oligonucleotide can inhibit the transdifferentiation of fibroblast towards myofibroblast in the pathological process of bleomycin-induced pulmonary fibrosis in mice.

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Inducible Nitric Oxide Synthase (iNOS) and Nitric Oxide (NO) are Important Mediators of Reflux-induced Cell Signalling in Esophageal Cells

Cited by 51 publications

References 44 publications

Toxicological Effect of Manganese on NF-κB/iNOS-COX-2 Signaling Pathway in Chicken Testes

Toxicological Effect of Manganese on NF-κB/iNOS-COX-2 Signaling Pathway in Chicken Testes

Endothelial Nitric Oxide Synthase and Superoxide Mediate Hemodynamic Initiation of Intracranial Aneurysms

The effect of NF-κB antisense oligonucleotide on transdifferentiation of fibroblast in lung tissue of mice injured by bleomycin

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