Inhibition of lipopolysaccharide‐inducible nitric oxide synthase, TNF‐α and COX‐2 expression by sauchinone effects on I‐κBα phosphorylation, C/EBP and AP‐1 activation

Lee, Ae Kyung; Sung, Sang Hyun; Kim, Young Choong; Kim, Sang Geon

doi:10.1038/sj.bjp.0705231

Cited by 259 publications

(151 citation statements)

References 34 publications

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“…COX-2 and NOS-2 are known to be regulated in the same manner in some systems through common mediators including C/EBPs (49,50). We show that CO inhibited NOS-2 mRNA and protein induction, as well as nitrite production, which was accompanied by decreased binding activity of C/EBP consensus sequence of the murine nos-2 promoter, strengthening the argument that CO modulation of C/EBPs is important in its anti-inflammatory effect.…”

Section: Discussionsupporting

confidence: 70%

CCAAT/Enhancer-Binding Protein Mediates Carbon Monoxide–Induced Suppression of Cyclooxygenase-2

Suh

Yang

et al. 2006

Am J Respir Cell Mol Biol

102

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Cyclooxygenase-2 (COX-2) is a key enzyme involved in the inflammatory process that is rapidly induced in macrophages in response to LPS. Carbon monoxide (CO), a byproduct of heme oxygnease-1, can suppress proinflammatory response in various in vitro and in vivo models of inflammation. This study was undertaken to examine whether CO can regulate (and if so, to delineate the mechanism by which CO regulates) LPS-induced COX-2 expression in macrophages. RAW 264.7 murine macrophages were stimulated with LPS (0-10 ng/ml) with or without CO (500 ppm). Northern and Western blot analysis was done. Progstaglandin E 2 and nitrite concentration was measured from cell culture supernatant. Electrophoretic mobility shift assay was performed to assess nuclear factor binding. CO downregulated LPS-induced COX-2 mRNA and protein expression. CO also inhibited LPS-induced prostaglandin E 2 secretion (P Ͻ 0.05). CO also decreased LPS-induced CCAAT/enhancer-binding protein (C/EBP) ␤ and ␦ protein expression in LPS-treated RAW 264.7 cells. Gel shift analysis revealed that CO treatment decreased LPSinduced activation of protein binding to C/EBP consensus oligonucleotides of murine cyclooxygenase-2 promoter. CO also decreased LPS-induced nitric oxide synthase-2 protein expression and nitrite production, and decreased LPS-induced activation of protein binding to C/EBP consensus oligonucleotides of murine nitric oxide synthase-2 promoter. CO may act as an important regulator of inflammation by virtue of its ability to regulate C/EBPs. Keywords: heme oxygenase; lipopolysaccharides; nitric oxide synthase Heme oxygenase-1 (HO-1) is a microsomal enzyme responsible for degradation of heme, generating biliverdin, iron, and carbon monoxide (CO) (1). HO-1 can be induced by a wide variety of stimuli, and the enzyme is involved in cellular and tissue defense against oxidative stress possessing potent anti-inflammatory properties (2, 3). There is growing interest in the role of CO in the anti-inflammatory and cytoprotective function of HO-1 (4-7), but the pathways involved in the anti-inflammatory effect of CO are poorly understood. CO can modulate mitogen-activated protein kinase (5) and guanylate cyclase/3Ј,5Ј-guanylate cyclic monophospate (cGMP) pathway (8) to inhibit secretion of proinflammatory cytokines. CO also modulates several transcription factors, including NF-B (4, 6) and activating protein-1 (4), which are involved in inflammation. But whether other pathways or molecules are involved in the anti-inflammatory effect of CO is not known.

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Section: Discussionsupporting

confidence: 70%

CCAAT/Enhancer-Binding Protein Mediates Carbon Monoxide–Induced Suppression of Cyclooxygenase-2

Suh

Yang

et al. 2006

Am J Respir Cell Mol Biol

102

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“…In the present work, we first determined the effect of DMA on NO −2 secretion as an initial evaluation of its antiinflammatory potential in LPS-stimulated RAW 264.7 cells (43)(44)(45). Our data reveal that DMA at 10 mM results in a 21% reduction in NO −2 levels in LPS-induced RAW 264.7 cells, as compared with the LPS control.…”

Section: Dma Inhibits the Transcriptional Activity Of Nf-κb But Not Amentioning

confidence: 91%

N,N-Dimethylacetamide Significantly Attenuates LPS- and TNFα-Induced Proinflammatory Responses Via Inhibition of the Nuclear Factor Kappa B Pathway

Pekson

Poltoratsky

Gorasiya

et al. 2016

Mol Med

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Previously, we have shown that N,N-dimethylacetamide (DMA) prevents inflammation-induced preterm birth in a murine model, inhibits lipopolysaccharide (LPS)-induced increases in placental proinflammatory cytokines and upregulates the antiinflammatory cytokine interleukin-10 (IL-10). However, DMA's mechanism of action remains to be elucidated. In the current study, we investigate how DMA produces its antiinflammatory effect. Using in vitro and ex vivo models, we show that DMA suppresses secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264.7 cells, TNFα-challenged JEG-3 cells and LPS-stimulated human placental explants. DMA significantly attenuated secretion of TNFα, IL-6, IL-10 and granulocyte macrophage colony stimulating factor (GM-CSF) from LPS-stimulated RAW 264.7 cells; IL-6 secretion from TNFα-stimulated JEG-3 cells; and TNFα, IL-6, IL-10, GM-CSF and Interleukin-8 (IL-8) from LPS-stimulated human placental explants. We further investigated whether DMA's effect on cytokine expression involves the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. DMA (10 mM) significantly inhibited degradation of nuclear factor of kappa light polypeptide gene enhancer in B cell inhibitor α (IκBα) in LPS-stimulated RAW 264.7 cells, but there was no significant change in the expression of phosphorylated or native forms of downstream proteins in the MAPK pathway. In addition, DMA significantly attenuated luciferase activity in cells co-transfected with NF-κB-Luc reporter plasmid, but not with AP-1-Luc or CEBP-Luc reporters. Overall, our findings suggest that the antiinflammatory activity of DMA is mediated by inhibition of the NF-κB pathway via decreased IκBα degradation.

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“…In addition, apoptotic cell death induced by exposure to cyanide can be inhibited by selective COX-2 inhibition [11,12] . Oxidative stress-induced COX-2 expression can be prevented in numerous cell types, including neurons, by free radical scavengers.…”

Section: Introductionmentioning

confidence: 99%

Isochaihulactone protects PC12 cell against H2O2 induced oxidative stress and exerts the potent anti-aging effects in D-galactose aging mouse model

Lin²,

et al. 2010

Acta Pharmacol Sin

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Aim: To investigate the effect of isochaihulactone (also known as K8), a lignan compound of Bupleurum scorzonerifolium, on H 2 O 2 -induced cytotoxicity in neuronally differentiated PC12 cells (nPC12). Methods: Viability of neuronal PC12 cells was measured using MTT assay. Protein expression was determined by Western blot. Apoptotic cells was determined using TUNEL assay. D-galactose aging mice were used as a model system to study the anti-oxidant effects of isochaihulactone in vivo. Results: Pretreatment with isochaihulactone (5-10 μmol/L) increased cell viability and decreased membrane damage, generation of reactive oxygen species and degradation of poly (ADP-ribose) polymerase in H 2 O 2 -treated nPC12 cells and also decreased the expression of cyclooxygenase-2, via downregulation of NF-kappaB, resulting in a decrease in lipid peroxidation. The results suggest that isochaihulactone is a potential antioxidant agent. In a murine aging model, in which chronic systemic exposure to D-galactose (D-gal) causes the acceleration of senescence, administration of isochaihulactone (10 mg·kg -1 ·d -1 , sc) for 7 weeks concomitant with D-gal injection significantly increased superoxide dismutase and glutathione peroxidase activities and decreased the MDA level in plasma. Furthermore, H&E staining to quantify cell death within hippocampus showed that percentage of pyknotic nuclei in the D-gal-treated mice were much higher than in control. Conclusion: The results suggest that isochaihulactone exerts potent anti-aging effects against D-gal in mice possibly via antioxidative mechanisms.

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Inhibition of lipopolysaccharide‐inducible nitric oxide synthase, TNF‐α and COX‐2 expression by sauchinone effects on I‐κBα phosphorylation, C/EBP and AP‐1 activation

Cited by 259 publications

References 34 publications

CCAAT/Enhancer-Binding Protein Mediates Carbon Monoxide–Induced Suppression of Cyclooxygenase-2

CCAAT/Enhancer-Binding Protein Mediates Carbon Monoxide–Induced Suppression of Cyclooxygenase-2

N,N-Dimethylacetamide Significantly Attenuates LPS- and TNFα-Induced Proinflammatory Responses Via Inhibition of the Nuclear Factor Kappa B Pathway

Isochaihulactone protects PC12 cell against H2O2 induced oxidative stress and exerts the potent anti-aging effects in D-galactose aging mouse model

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