Effect of erythromycin on cigarette-induced histone deacetylase protein expression and nuclear factor-κB activity in human macrophages in vitro

Li, Meihua; Zhong, Xiaoning; Zhou, He; Wen, Mingzhi; Li, Jiaquan; Peng, Xinyan; Liu, Guangnan; Deng, Jingmin; Zhang, Jianquan; Bai, Jing

doi:10.1016/j.intimp.2011.12.022

Cited by 47 publications

(47 citation statements)

References 53 publications

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“…4D), which indicated that EPREGO potentially suppresses the NF-κB signaling pathway, thus, reducing inflammatory response-mediated NO and IL-6 production. These results are consistent with previous reports demonstrating that the NF-κB signaling pathway is essential for LPS-stimulated cytokine production (27)(28)(29)(30) in macrophages.…”

Section: Discussionsupporting

confidence: 94%

16α, 17α-epoxypregnenolone-20-oxime inhibits NO and IL-6 production in LPS-treated RAW264.7 cells

Sun

Han

et al. 2016

Molecular Medicine Reports

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Abstract. It has previously been repor ted t hat 16α, 17α-epoxypregnenolone-20-oxime (EPREGO) exerts an inhibitory effect on nitric oxide (NO) production and inducible NO synthase (iNOS) expression in microglia. The present study aimed to investigate the effects of EPREGO on the lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 macrophage cells, and to determine the underlying molecular mechanisms using western blot analysis, enzyme-linked immunosorbent assays and fluorescence-activated cell sorting. The present study demonstrated that LPS-induced production of NO and interleukin (IL)-6, and the protein expression levels of iNOS, were reduced by EPREGO in a dose-and time-dependent manner, whereas, EPREGO did not affect tumor necrosis factor-α production. In addition, EPREGO suppressed LPS-induced cellular reactive oxygen species production and phagocytosis. Furthermore, EPREGO significantly inhibited the LPS-induced activation of mitogen-activated protein kinases and inhibitor of κB α degradation in LPS-stimulated RAW264.7 cells, thus resulting in modulation of the production of NO and IL-6. Taken together, these results suggest that EPREGO exhibits anti-inflammatory activity in macrophages, thus validating the hypothesis that EPREGO may be useful as a therapeutic agent for the treatment of macrophage-mediated inflammation. IntroductionMacrophages, which are critical effector cells, contribute to the innate immune response against infection. Macrophages are considered the most efficient pathogen scavengers, and are the main source of proinflammatory mediators and cytokines, including nitric oxide (NO), interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Proinflammatory mediators are essential for inducing inflammation at the site of infection and for fighting pathogenic infections (1,2). However, the excessive production of proinflammatory cytokines has severe consequences, including tissue damage and septic shock (3,4). Therefore, suppressing the synthesis or release of proinflammatory cytokines and mediators is a potential therapeutic strategy for the treatment of septic shock-like diseases associated with inappropriately amplified inflammation.Several intracellular signaling pathways, including the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways, are activated in lipopolysaccharide (LPS)-induced macrophages, and regulate inflammatory actions and immune responses. In macrophages, the MAPK signaling pathway is one of the most extensively investigated intracellular signaling cascades involved in the LPS-induced inflammatory response (5-8). The MAPK pathway is comprised of at least three signaling components: Extracellular signal-regulated kinases 1/2 (ERK 1/2); c-Jun N-terminal kinase (JNK); and p38 MAPK, all of which have been demonstrated to induce the release of immune-related cytotoxic factors and proinflammatory cytokines (9-11). Furthermore, NF-κB is important for controlling innate and adaptive immunity, and for regulating the expression of various genes d...

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Section: Discussionsupporting

confidence: 94%

16α, 17α-epoxypregnenolone-20-oxime inhibits NO and IL-6 production in LPS-treated RAW264.7 cells

Sun

Han

et al. 2016

Molecular Medicine Reports

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“…HDAC2 expression and activity is regulated through PI3K-␦/Akt and, specifically, a decrease in PAkt levels may increase the expression of HDAC2 (25). We have previously shown that pretreatment of U937 cells with EM reversed CSE-induced reductions in HDAC1, -2, and -3 protein expression, with the most prominent effects observed on HDAC2 (22). Decreased HDAC2 activity via CSE exposure may be related to corticosteroid insensitivity.…”

Section: Discussionmentioning

confidence: 96%

“…The supernatants were obtained and stored in Ϫ80°C prior to experimental use. IL-8 levels were quantified with an ELISA (R&D Systems, Minneapolis, MN), as previously reported (22). The IL-8 inhibition ratio was calculated by use of Microsoft Excel, version 2003.…”

Section: Methodsmentioning

confidence: 99%

“…Previously, studies from our laboratory have shown that 6 mo of EM treatment in COPD patients was sufficient to reduce airway inflammation and COPD-related exacerbations (16). Moreover, EM administration reversed the CSE-induced decreased expression of HDAC2 (22). Because corticosteroid receptor function is reduced in COPD patients, treatment with corticosteroids does not have a significant impact on inflammation or HDAC2 activity.…”

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confidence: 92%

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Combination of erythromycin and dexamethasone improves corticosteroid sensitivity induced by CSE through inhibiting PI3K-δ/Akt pathway and increasing GR expression

Sun

Zhang

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Corticosteroid insensitivity, which is induced by cigarette smoke extract (CSE), is a significant barrier when treating chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been shown to have an anti-inflammatory role in some chronic airway inflammatory diseases, particularly diffuse panbronchiolitis and cystic fibrosis. Here, we explored whether the combination therapy of EM and dexamethasone (Dex) reverses corticosteroid insensitivity and investigated the molecular mechanism by which this occurs. We demonstrated that the combination of EM and Dex restored corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from COPD patients and U937 cells after CSE exposure. Moreover, pretreatment with 10, 50, or 100 g/ml EM reversed the HDAC2 protein reduction induced by CSE exposure in a dose-dependent manner. U937 cells exposed to CSE show a reduction in histone deacetylase (HDAC) activity, which was potently reversed by EM or combination treatment. Although 10 and 17.5% CSE increased phosphorylated Akt (PAkt) expression in a concentration-dependent manner, preapplication of EM and the combination treatment in particular blocked this PAkt increase. Total Akt levels were unaffected by CSE or EM treatments. Furthermore, the combination treatment enhanced glucocorticoid receptor (GR)␣ expression. Our results demonstrate that the combination therapy of EM and Dex can restore corticosteroid sensitivity through inhibition of the PI3K-␦/Akt pathway and enhancing GR␣ expression.

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“…Trisiklik antidepresan nortriptilin HDAC aktivitesini artırarak kortikosteroid etkisini geri kazandırır (31). Eritromisin, HDAC1, HDAC2 ve HDAC3 redüksiyonunu, NF-κB aktivitesini inhibe eder (32). Flavonoid olan baisalin HDAC2 fosforilasyonunun inhibisyonu ile steroid direncini önlemektedir (33).…”

Section: Sigara -Oksidatif Stresunclassified

Epigenetic and current treatment approaches in chronic obstructive pulmonary disease

Duru

2016

Tuberk Toraks

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SUMMARY Epigenetic and current treatment approaches in chronic obstructive pulmonary disease Epigenetics mechanisms such as DNA methylation, histone acetylation and non-coding RNAs may play are a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Researchs with regard epigenetic in COPD can shed light on pathogenes and may be relevant in the development of novel targeted therapies. The aim of this article is to review epigenetic mechanisms new treatments approaches in COPD.

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Effect of erythromycin on cigarette-induced histone deacetylase protein expression and nuclear factor-κB activity in human macrophages in vitro

Cited by 47 publications

References 53 publications

16α, 17α-epoxypregnenolone-20-oxime inhibits NO and IL-6 production in LPS-treated RAW264.7 cells

16α, 17α-epoxypregnenolone-20-oxime inhibits NO and IL-6 production in LPS-treated RAW264.7 cells

Combination of erythromycin and dexamethasone improves corticosteroid sensitivity induced by CSE through inhibiting PI3K-δ/Akt pathway and increasing GR expression

Epigenetic and current treatment approaches in chronic obstructive pulmonary disease

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