Short-term roxithromycin treatment attenuates airway inflammation via MAPK/NF-κB activation in a mouse model of allergic asthma

Ci, Xinxin; Chu, Xiao; Xue, Xiaonan; Li, Hongyu; Deng, Xuming

doi:10.1007/s00011-012-0470-6

Cited by 20 publications

(7 citation statements)

References 45 publications

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“…The results of the present study provided novel evidence for the protective effect of ERY on the development of emphysema induced by CS via regulation of the expression of MMP-2, MMP-9 and TIMP-1, and improvement of the inflammation of the lungs via MAPK/NF-κB activation, thus indicating its potential use as a therapeutic agent for the treatment of COPD. Similar studies on the potential signaling pathway of the macrolides were performed in an asthma model in vivo (21) or in inflammation-stimulated cells in vitro (22). MAPKs, together with NF-κB activation, are the kinases that are activated in airway epithelial cells and macrophages exposed to CS extracts, which induces the expression of various pro-inflammatory chemokines and cytokines (17).…”

Section: Discussionmentioning

confidence: 88%

Erythromycin attenuates metalloprotease/anti-metalloprotease imbalance in cigarette smoke-induced emphysema in rats via the mitogen-activated protein kinase/nuclear factor-κB activation pathway

Zhou

Hou

2017

Molecular Medicine Reports

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The present study investigated whether erythromycin (ERY) reduces cigarette smoke (CS)-induced emphysema in rats and aimed to determine the anti-inflammatory effect of ERY, which may identify potential treatments for chronic obstructive pulmonary disease. Furthermore, the current study focused on the potential effects on the imbalance between matrix metalloprotease (MMP) and anti-MMP activity, the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-κB (NF-κB) signaling pathway. Wistar rats were divided into the following three groups (n=12 each): control (ERY vehicle only, without any CS exposure), CS (animals were exposed to CS for 12 weeks) and CS + ERY (animals were exposed to CS for 12 weeks and received 100 mg/kg/day ERY). The recruitment of inflammatory cells into the bronchoalveolar lavage fluid (BALF) and the histopathology of lung tissue from all groups was evaluated to grade the severity of the emphysema. The expression of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase-1 was evaluated by immunohistochemistry and western blotting. The activation of MAPKs, NF-κB and inhibitor of NF-κB (IκBα), in lung tissues was examined by western blotting. Treatment with ERY resulted in fewer inflammatory cells and cytokines in the BALF, and fewer emphysema-associated changes in the lungs compared with control. The stimulus of CS promoted the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and p38, but not c-Jun NH2-terminal kinase, thereby inducing the activation of the ERK/MAPK signaling pathway in rats. Furthermore, CS exposure increased the expression of NF-κB and decreased the expression of IκBα. The levels of phosphorylated ERK1/2 and p38 were significantly reduced in rats with CS-induced emphysema when treated with ERY compared with the CS group. The results of the present study therefore indicate that oral administration of ERY may suppress CS-induced emphysema by regulating inflammatory cytokines and the MMP/anti-MMP imbalance via the MAPK/NF-κB pathway.

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Section: Discussionmentioning

confidence: 88%

Erythromycin attenuates metalloprotease/anti-metalloprotease imbalance in cigarette smoke-induced emphysema in rats via the mitogen-activated protein kinase/nuclear factor-κB activation pathway

Zhou

Hou

2017

Molecular Medicine Reports

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“…20,21 Roxithromycin was shown to exert its anti-inflammatory effect by inhibiting the activation of NF-κB in a mouse model of allergic asthma. 22 Although a previous study demonstrated that roxithromycin suppressed colitis in IL-10-deficient mice, the basic mechanism remains unclear. Therefore, we explored the effect of roxithromycin in reducing intestinal inflammation.…”

Section: Discussionmentioning

confidence: 99%

Roxithromycin inhibits nuclear factor kappaB signaling and endoplasmic reticulum stress in intestinal epithelial cells and ameliorates experimental colitis in mice

Choi

Koh

Lee

et al. 2015

Exp Biol Med (Maywood)

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Roxithromycin is known to have anti-inflammatory and immunoregulatory activity. However, little information is available on the effect of roxithromycin in intestinal inflammation. The aim of this study was to investigate the effect of roxithromycin on NF- κB signaling and ER stress in intestinal epithelial cells (IECs) and the effect of roxithromycin on dextran sulfate sodium (DSS)-induced acute colitis in a murine model. HCT116 cells and COLO205 cells were pretreated with roxithromycin and then stimulated with tumor necrosis factor-α (TNF-α). Interleukin (IL)-8 expression was determined by real-time reverse transcription-polymerase chain reaction. Nuclear factor kappaB (NF-κB) DNA-binding activity and IκB phosphorylation/degradation were evaluated by electrophoretic mobility shift assay and Western blot analysis. The molecular markers of endoplasmic reticulum stress, including p-JNK, phosphorylated eukaryotic initiation factor 2 (p-eIF2α), C/EBP homologous protein (CHOP), and X-box binding protein 1 (XBP1) were evaluated using western blotting and PCR. Mice were given 4% DSS for five days with or without roxithromycin. Primary IECs were isolated from mice with DSS-induced colitis. Roxithromycin significantly inhibited the upregulated expression of IL-8. Pretreatment with roxithromycin markedly attenuated NF-κB DNA-binding activity and IκB phosphorylation/degradation. CHOP and XBP1 mRNA expression were enhanced in the presence of TNF-α, and it was dampened by pretreatment of roxithromycin. c-Jun-N-terminal kinase (JNK) phosphorylation and the level of p-eIF2α were also downregulated by the pretreatment of roxithromycin. Roxithromycin significantly reduced the severity of DSS-induced murine colitis, as assessed by the disease activity index, colon length, and histology. In addition, the DSS-induced phospho-IκB kinase activation was significantly decreased in roxithromycin-pretreated mice. Finally, IκB degradation was reduced in primary IECs from mice treated with roxithromycin. These results suggest that roxithromycin may have potential usefulness in the treatment of inflammatory bowel disease.

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“…Understanding the pathogenesis and mechanisms of allergic asthma is important for finding appropriate therapeutic targets so that patients can receive symptomatic treatment [45]. Although there are treatments that are currently available for the management of asthma targeted at dampening airway inflammation and relaxing airway smooth muscles, including inhaled corticosteroids and β 2 agonists, they do not eliminate the occurrence of disease because they do not alter the underlying pathology [46].…”

Section: Discussionmentioning

confidence: 99%

Treatment with Pyranopyran-1, 8-Dione Attenuates Airway Responses in Cockroach Allergen Sensitized Asthma in Mice

Park

Jung

et al. 2014

PLoS ONE

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Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. Viticis Fructus (VF) has long been used in China and Korea as a traditional herbal remedy for treating various inflammatory diseases. Previously, we have isolated a novel phytochemical, pyranopyran-1, 8-dione (PPY), from VF. This study was conducted to evaluate the ability of PPY to prevent airway inflammation and to attenuate airway responses in a cockroach allergen-induced asthma model in mice. The mice sensitized to and challenged with cockroach allergen were treated with oral administration of PPY. The infiltration of total cells, eosinophils and lymphocytes into the BAL fluid was significantly inhibited in cockroach allergen-induced asthma mice treated with PPY (1, 2, or 10 mg/kg). Th2 cytokines and chemokine, such as IL-4, IL-5, IL-13 and eotaxin in BAL fluid were also reduced to normal levels following treatment with PPY. In addition, the levels of IgE were also markedly suppressed after PPY treatment. Histopathological examination demonstrated that PPY substantially inhibited eosinophil infiltration into the airway, goblet cell hyperplasia and smooth muscle hypertrophy. Taken together, these results demonstrate that PPY possesses a potent efficacy on controlling allergic asthma response such as airway inflammation and remodeling.

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Short-term roxithromycin treatment attenuates airway inflammation via MAPK/NF-κB activation in a mouse model of allergic asthma

Cited by 20 publications

References 45 publications

Erythromycin attenuates metalloprotease/anti-metalloprotease imbalance in cigarette smoke-induced emphysema in rats via the mitogen-activated protein kinase/nuclear factor-κB activation pathway

Erythromycin attenuates metalloprotease/anti-metalloprotease imbalance in cigarette smoke-induced emphysema in rats via the mitogen-activated protein kinase/nuclear factor-κB activation pathway

Roxithromycin inhibits nuclear factor kappaB signaling and endoplasmic reticulum stress in intestinal epithelial cells and ameliorates experimental colitis in mice

Treatment with Pyranopyran-1, 8-Dione Attenuates Airway Responses in Cockroach Allergen Sensitized Asthma in Mice

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