Nitric Oxide Production and Signaling in Inflammation

Korhonen, Riku; Lahti, Aleksi; Kankaanranta, Hannu; Moilanen, Eeva

doi:10.2174/1568010054526359

Cited by 844 publications

(663 citation statements)

References 191 publications

(240 reference statements)

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“…This indicates that it is a key contributor to the anti-inflammatory activity of rhubarb. NO is a well-known pro-inflammatory cytokine involved in many inflammatory diseases (Guzik et al, 2003) and is produced in high amounts by the iNOS protein that is induced by microbial products, such as LPS (Korhonen et al, 2005). Our data indicate that aloe-emodin inhibits the transcription and protein expression of iNOS.…”

Section: Discussionmentioning

confidence: 48%

Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages

Zhang

Meng

et al. 2014

Journal of Ethnopharmacology

166

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Section: Discussionmentioning

confidence: 48%

Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages

Zhang

Meng

et al. 2014

Journal of Ethnopharmacology

166

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“…Excessive production of nitric oxide is thought to play a role in inflammatory diseases (reviewed in [1]). Nitric oxide is generated from L-arginine by the catalytic reaction of different isoforms of nitric oxide synthase (NOS), including neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS).…”

Section: Introductionmentioning

confidence: 99%

Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes

et al. 2007

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Aims/hypothesis Diabetes results in the upregulation of the production of several components of the inflammatory response in the retina, including inducible nitric oxide synthase (iNOS). The aim of this study was to investigate the role of iNOS in the pathogenesis of the early stages of diabetic retinopathy using iNOS-deficient mice (iNos −/− ). Materials and methods iNos −/− mice and wild-type (WT; C57BL/6J) mice were made diabetic with streptozotocin or kept as non-diabetic controls. Mice were killed at different time points after the induction of diabetes for assessment of vascular histopathology, cell loss in the ganglion cell layer (GCL), retinal thickness, and biochemical and physiological abnormalities. Results The concentrations of nitric oxide, nitration of proteins, poly(ADP-ribose) (PAR)-modified proteins, endothelial nitric oxide synthase, prostaglandin E 2 , superoxide and leucostasis were significantly (p<0.05) increased in retinas of WT mice diabetic for 2 months compared with nondiabetic WT mice. All of these abnormalities except PARmodified proteins in retinas were inhibited (p<0.05) in diabetic iNos −/− mice. The number of acellular capillaries and pericyte ghosts was significantly increased in retinas from WT mice diabetic for 9 months compared with nondiabetic WT controls, these increases being significantly inhibited in diabetic iNos −/− mice (p<0.05 for all). Retinas from WT diabetic mice were significantly thinner than those from their non-diabetic controls, whereas diabetic iNos −/− mice were protected from this abnormality. We found no evidence of cell loss in the GCL of diabetic WT or iNos −/− mice. Deletion of iNos had no beneficial effect on diabetes-induced abnormalities on the electroretinogram.Conclusions/interpretation We demonstrate that the inflammatory enzyme iNOS plays an important role in the pathogenesis of vascular lesions characteristic of the early stages of diabetic retinopathy in mice.

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“…It has cytotoxic and cytostatic effects, which are beneficial in host defence against pathogenic microbes. In inflammatory diseases, the regulatory, pro-inflammatory and destructive effects of NO modulate the responses also in host tissues (Moilanen et al, 1999;Abramson et al, 2001;Korhonen et al, 2005) and inhibitors of iNOS have been found to be beneficial in various models of inflammatory diseases (Vallance and Leiper, 2002). High amounts of NO are produced through the inducible nitric oxide synthase (iNOS) pathway in response to proinflammatory cytokines and bacterial products.…”

Section: Introductionmentioning

confidence: 99%

“…High amounts of NO are produced through the inducible nitric oxide synthase (iNOS) pathway in response to proinflammatory cytokines and bacterial products. Expression of iNOS has been shown to be regulated both at transcriptional and post-translational levels in activated macrophages, but many of the mechanisms are still unknown (MacMicking et al, 1997;Alderton et al, 2001;Kleinert et al, 2003;Aktan, 2004;Korhonen et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

PPARα agonists inhibit nitric oxide production by enhancing iNOS degradation in LPS‐treated macrophages

Leppänen

Sareila

et al. 2007

British J Pharmacology

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Background and purpose: Nitric oxide (NO) production through the inducible nitric oxide synthase (iNOS) pathway is increased in response to pro-inflammatory cytokines and bacterial products. In inflammation, NO has pro-inflammatory and regulatory effects. Peroxisome proliferator-activated receptors (PPARs), members of the nuclear steroid receptor superfamily, regulate not only metabolic but also inflammatory processes. The aim of the present study was to investigate the role of PPARa in the regulation of NO production and iNOS expression in activated macrophages. Experimental approach: The effects of PPARa agonists were investigated on iNOS mRNA and protein expression, on NO production and on the activation of transcription factors NF-kB and STAT1 in J774 murine macrophages exposed to bacterial lipopolysaccharide (LPS). Key results: PPARa agonists GW7647 and WY14643 reduced LPS-induced NO production in a dose-dependent manner as measured by the accumulation of nitrite into the culture medium. However, PPARa agonists did not alter LPS-induced iNOS mRNA expression or activation of NF-kB or STAT1 which are important transcription factors for iNOS. Nevertheless, iNOS protein levels were reduced by PPARa agonists in a time-dependent manner. The reduction was markedly greater after 24 h incubation than after 8 h incubation. Treatment with the proteasome inhibitors, lactacystin or MG132, reversed the decrease in iNOS protein levels caused by PPARa agonists. Conclusions and implications:The results suggest that PPARa agonists reduce LPS-induced iNOS expression and NO production in macrophages by enhancing iNOS protein degradation through the proteasome pathway. The results offer an additional mechanism underlying the anti-inflammatory effects of PPARa agonists.

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Nitric Oxide Production and Signaling in Inflammation

Cited by 844 publications

References 191 publications

Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages

Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages

Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes

PPARα agonists inhibit nitric oxide production by enhancing iNOS degradation in LPS‐treated macrophages

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