Lipopolysaccharide and proinflammatory cytokines require different astrocyte states to induce nitric oxide production

Kozuka, Nagisa; Itofusa, Rurika; Kudo, Yoshihisa; Morita, Mitsuhiro

doi:10.1002/jnr.20671

Cited by 31 publications

(15 citation statements)

References 56 publications

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“…At the same time, COX-2 and iNOS could activate each other and further promote the production of PGE 2 and NO (Corbett et al 1993;Salvemini et al 1993;Blanco & Lotz 1995;Hajjar et al 1995;Salvemini et al 1996;Tetsuka et al 1996). Moreover, the increased production of cytokines, such as IL-1b and TNF-a, could also stimulate PGE 2 and NO production (Kozuka et al 2005;Yu et al 2010). The change trend of PGE 2 , NO, COX-2 and iNOS in this study was similar to these previous studies.…”

Section: Effects Of Voas On Cytokines Inflammatory Mediators and Infsupporting

confidence: 88%

Effects of volatile oils ofAngelica sinensison an acute inflammation rat model

Hua

et al. 2016

Pharmaceutical Biology

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Context Despite several pharmacological studies of volatile oils of Angelica sinensis (Oliv.) Diels (Umbelliferae) (VOAS), its anti-inflammatory mechanism remains unknown. Objective The study investigates the effects of VOAS on the lipopolysaccharide (LPS)-induced acute inflammation rat model and analyzes its possible anti-inflammatory mechanisms. Materials and methods Fourty rats were randomly divided into the control, model, VOAS and dexamethasone (Dex) groups. The VOAS and Dex groups were given VOAS (0.176 mL/kg) and Dex (40 mg/kg), respectively. Rats in all groups except the control group were intraperitoneally injected with LPS (100 mg/kg), their exterior behaviour and liver pathological changes were observed, and the level of white blood cell (WBC), the number of neutrophils (NE)%, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP), tumour necrosis factor (TNF-a), interleukin (IL)-1b, IL-6, IL-10, histamine (HIS), 5-hydroxytryptamine (5-HT), nitric oxide (NO), prostaglandin E 2 (PGE 2 ), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) were detected.Results Compared with the model group, VOAS and Dex significantly accelerated the recovery of the exterior behaviour, the liver pathological changes of rats, and increased the level of IL-10, but decreased the level of WBC, NE%, GOT, GPT, ALP, TNF-a, IL-1b, IL-6, HIS, 5-HT, NO, PGE 2 , iNOS and COX-2 (p50.05). Conclusion VOAS exhibits anti-inflammatory and liver protection effects by inhibiting the secretion of the pro-inflammatory cytokines (TNF-a, IL-1b and IL-6), the inflammatory mediators (HIS, 5-HT, PGE 2 and NO), the inflammation-related enzymes (iNOS and COX-2), as well as promoting the production of the anti-inflammatory cytokines IL-10. ARTICLE HISTORY

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Section: Effects Of Voas On Cytokines Inflammatory Mediators and Infsupporting

confidence: 88%

Effects of volatile oils ofAngelica sinensison an acute inflammation rat model

Hua

et al. 2016

Pharmaceutical Biology

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“…It is not certain, however, if the growth of cancer cells and thereafter space occupation by the tumor mass could directly lead to any neuronal degeneration or even neuronal death. iNOS, a protein mediating the synthesis of NO, is found in brain microglia and peripheral macrophages (24) and in astrocytes (25,26). Normally, activated microglia show a significant increase in the expression level of iNOS (27).…”

Section: Discussionmentioning

confidence: 99%

Differential Reactions of Microglia to Brain Metastasis of Lung Cancer

Wang

Zhang

et al. 2006

Mol Med

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The brain is a common metastatic site for various types of cancers, especially lung cancer. Patients with brain metastases have a poor prognosis in spite of radiotherapy and/or chemotherapy. It is postulated that immune cells in the brain may play a major role in cancer metastasis, dormancy, and relapse. Although microglia may serve as a major component in the brain immune system, the interaction between metastatic cancer cells and microglia is still largely unknown and remains to be elucidated. In this study, we have investigated microglial reactions in brain tissues with metastatic lung cancer cells and evaluated the cytotoxic effects of lipopolysaccharide (LPS)-activated microglia on metastatic lung cancer cells in vitro. In the vicinity of metastatic lung cancer mass in the brain, microglia showed signs of significant activation. There was an obvious increase in the number of microglia labeled with ionized calcium binding adaptor molecule 1 (Iba-1) antibody, a specific marker of microglia. The microglia were observed to form a clear boundary between the tumor mass and normal brain tissue. In the region where the tumor mass was situated, only a few microglia expressed inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α), indicating differential activation in those microglia. The supernatant from LPS-activated microglia induced apoptosis of metastatic lung cancer cells in vitro in a dose-and time-dependent manner. However, at lower concentrations of activated microglial supernatant, trophic effects on cancer cells were observed, some lung cancer cells being insensitive to microglial cytotoxicity. Together with the observation that TNF-α alone induced proliferation of the tumor cells, the findings provide possible clues to the mechanism involved in metastasis of lung cancer cells to the brain.

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“…Excessive NO can induce neuronal cell damage by disrupting the function of the neuronal mitochondrial electron transport chain (5). Inflammation is also characterized by increased production of cytokines, such as IL-1ß and TNF-·, which also act to stimulate iNOS and NO production (6). Hence, modulation of NO production, glial signalling cascades and pro-inflammatory cytokines might result in suppression of neuro-inflammation and may ultimately protect against neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

Lee

2011

Int J Mol Med

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Abstract.Flavonoids have been reported to be potent antioxidants and beneficial in the treatment of oxidative stress-related diseases. Quercetin, a major flavonoid naturally occurring in plants, deserves attention because of its beneficial effects observed in various in vitro and in vivo neural damage models; however, the actions of quercetin are paradoxical. In an effort to confirm the neuroprotective effect of quercetin and to elucidate its mechanism of action, the neuroprotective effects of quercetin in PC12 cells and in zebrafish models were investigated. In this study, the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA), was used to induce neural damage in PC12 cells and zebrafish models. Pretreatment with quercetin offered neuroprotection against 6-OHDA-induced PC12 cell death. Moreover, quercetin could prevent 6-OHDA-induced PC12 cell apoptosis and 6-OHDA-stimulated dopaminergic neuron loss in zebrafish. Interestingly, quercetin was able to protect, but not rescue the dopaminergic neuron damage when zebrafish were treated with quercetin at different maturation stages of the blood brain barrier. A mechanistic study showed that quercetin could inhibit NO over-production and iNOS over-expression in PC12 cells and could down-regulate the over-expression of pro-inflammatory genes (e.g. IL-1ß, TNF-· and COX-2) in zebrafish, suggesting that these genes play a role in the neuroprotective effect of quercetin. The objective of this study was to provide a scientific rationale for the clinical use of quercetin, leading to its development as an effective therapeutic agent for the treatment of Parkinson's disease.

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Lipopolysaccharide and proinflammatory cytokines require different astrocyte states to induce nitric oxide production

Cited by 31 publications

References 56 publications

Effects of volatile oils ofAngelica sinensison an acute inflammation rat model

Effects of volatile oils ofAngelica sinensison an acute inflammation rat model

Differential Reactions of Microglia to Brain Metastasis of Lung Cancer

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

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