Inducible Nitric Oxide Synthase and Inflammatory Diseases

Zamora, Rubén; Vodovotz, Yoram; Billiar, Timothy R.

doi:10.1007/bf03401781

Cited by 431 publications

(338 citation statements)

References 324 publications

(158 reference statements)

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“…Inducible NO synthase, or iNOS, is the enzyme responsible for the production of NO, and its expression is often increased in tumor promotion (35,36). The triterpenoid CDDO-Im is one of the most potent known suppressors of iNOS (37) and was included as a control.…”

Section: Resultsmentioning

confidence: 99%

The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice

Cao

Royce

Risingsong

et al. 2016

Cancer Prevention Research

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LG101506 was originally synthesized to overcome some of the undesirable side effects of rexinoids. We compared the anticarcinogenic action of LG101506 and LG100268 and for the first time showed that both drugs are useful for prevention of lung cancer in A/J mice. These molecules markedly reduced tumor number, tumor size, and total tumor burden, when chronically administered to A/J mice that had been initiated with the mutagenic carcinogen, vinyl carbamate. Moreover, LG100268 synergized with the histone deacetylase inhibitor, vorinostat, for prevention of experimental lung cancer and enhanced the effect of carboplatin/paclitaxel for treatment of experimental lung cancer. Both rexinoids diminished the percentage of high-grade, highly malignant adenocarcinomas found at autopsy. In cell culture studies, the rexinoids exhibited potent anti-inflammatory properties at nanoMolar concentrations. These drugs suppressed the ability of lipopolysaccharide to stimulate the synthesis and secretion of nitric oxide and inflammatory cytokines and chemokines, such as IL6, IL1b, CXCL2, and CSF3, in macrophage-like RAW264.7 cells. The present results suggest that LG100268, LG101506, or a related rexinoid may have useful clinical applications in the field of oncology. Cancer Prev Res; 9(1);

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Section: Resultsmentioning

confidence: 99%

The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice

Cao

Royce

Risingsong

et al. 2016

Cancer Prevention Research

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“…Frequently, the over-production of NO in macrophages is due to the high expression of iNOS following persistent stimulation. Excessive NO is deleterious and may lead to severe diseases such as septic shock, inflammatory diseases and neurotoxicity [31,32] . The present study demonstrates that pretreatment of RAW264.7 cells with non-toxic concentrations of FLZ (1, 5, or 10 µmol/L) ( Table 1) for 30 min significantly inhibited the production of NO and the expression of the iNOS protein and mRNA (Figure 2A, 3).…”

Section: Discussionmentioning

confidence: 99%

Compound FLZ inhibits lipopolysaccharide-induced inflammatory effects via down-regulation of the TAK-IKK and TAK-JNK/p38MAPK pathways in RAW264.7 macrophages

Pang

Liu

2009

Acta Pharmacol Sin

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Aim:The aim of this study was to investigate the effect of the squamosamide derivative FLZ (N-2-(4-hydroxy-phenyl)-ethyl-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide) on lipopolysaccharide (LPS)-induced inflammatory mediator production and the underlying mechanism in RAW264.7 macrophages. Methods: RAW264.7 cells were preincubated with non-toxic concentrations of compound FLZ (1, 5, and 10 µmol/L) for 30 min and then stimulated with 10 μg/L LPS. The production of nitric oxide (NO), the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), and the activation of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways were examined. Results: FLZ significantly inhibited the LPS-induced production of NO, as well as the expression of iNOS and COX-2 at both the RNA and the protein levels in RAW264.7 cells. The LPS-induced increase in the DNA binding activity of NF-κB and activator protein 1 (AP-1), the nuclear translocation of NF-κB p65, the degradation of the inhibitory κBα protein (IκBα) and the phosphorylation of IκBα, IκB kinase (IKK) α/β, c-Jun NH 2 -terminal kinase (JNK) and p38 MAPKs were all suppressed by FLZ. However, the phosphorylation of extracellular signal-regulated kinase (ERK) was not affected. Further study revealed that FLZ inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), which is an upstream signaling molecule required for IKKα/β, JNK and p38 activation. Conclusion: FLZ inhibited the LPS-induced production of inflammatory mediators at least partly through the downregulation of the TAK-IKK and TAK-JNK/p38MAPK pathways.

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“…The NF-țB activation also induces the transcription of inducible nitric oxide synthase (iNOS), leading to the production of nitric oxide (NO), that is a pro-inflammatory mediator. The overproduction of NO contributes to the pathogenesis of septic shock and inflammatory diseases (Zamora et al, 2000;Guzik et al, 2003). Since the overproduction of these pro-inflammatory mediators raises and maintains inflammation, compounds targeting its expression and production through NF-țB and proteasome pathways are good candidates for attenuating inflammation.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-κB pathway inhibition: Contribution of chlorogenic acid

Francisco

Costa

Figueirinha

et al. 2013

Journal of Ethnopharmacology

111

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inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-κB pathway inhibition: contribution of chlorogenic acid, Journal of Ethnopharmacology, http://dx.doi.org/10. 1016/j.jep.2013.03.077 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Activation of nuclear factor-țB, a master regulator of inflammation, was investigated by Western blot and gene reporter assay. Proteasome activity was assessed using a fluorogenic peptide.Results: Cymbopogon citratus extract and its polyphenols inhibited the cytokine production on human macrophages. This supports the anti-inflammatory activity of Cy polyphenols in physiologically relevant cells. Concerning the effect on the activation of nuclear factor (NF)-țB pathway, the results pointed to an inhibition of LPS-induced NF-țB activation by Cy and PFs.Chlorogenic acid was identified, by HPLC/PDA/ESI-MS n , as the main phenolic acid of the Cy infusion, and it demonstrated to be, at least in part, responsible by that effect. Additionally, it was verified for the first time, that Cy and PFs inhibited the proteasome activity, a complex that controls NF-țB activation, having CGA a strong contribution. Conclusions:The results evidenced, for the first time, the anti-inflammatory properties of Cymbopogon citratus through proteasome inhibition and, consequently NF-țB pathway and cytokine expression. Additionally, Cy polyphenols, in particular chlorogenic acid, were highlighted as bio-active compounds.

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Inducible Nitric Oxide Synthase and Inflammatory Diseases

Abstract: The quoted references are mostly recent reviews of significant relevance. eNOS, endothelial isoform of nitric oxide synthase (NOS); iNOS, inducible form of NOS; NO, nitric oxide.

Cited by 431 publications

References 324 publications

The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice

The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice

Compound FLZ inhibits lipopolysaccharide-induced inflammatory effects via down-regulation of the TAK-IKK and TAK-JNK/p38MAPK pathways in RAW264.7 macrophages

Anti-inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-κB pathway inhibition: Contribution of chlorogenic acid

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