Montelukast inhibits inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes

Dong, Hua; Liu, Feng; Feng-yun, MA; Xu, Lianna; Pang, Linna; Li, Xuyan; Liu, Bo; Wang, Liang

doi:10.1016/j.intimp.2018.04.042

Cited by 21 publications

(16 citation statements)

References 35 publications

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“…Due to its anti-inflammatory effects, montelukast has also been found to be effective in stroke in vivo [9]. Besides, montelukast was found to have protective effects on other diseases, including rheumatoid arthritis, ischemia-reperfusion (I/R) injury, and Parkinson disease [10–12]. Moreover, studies have reported that montelukast has an activity of inhibiting the growth of tumor cells via inducing cell apoptosis [13,14].…”

Section: Introductionmentioning

confidence: 99%

Effect of Montelukast on Bronchopulmonary Dysplasia (BPD) and Related Mechanisms

2019

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BackgroundBronchopulmonary dysplasia (BPD) is a chronic lung disease common in preterm infants. Montelukast, an effective cysteinyl leukotriene (cysLT) receptor antagonist, has a variety of pharmacological effects and has protective effects against a variety of diseases. Currently, the efficacy and safety of montelukast sodium in treating BPD has been revealed, however, the precise molecular mechanism of the effect of montelukast on BPD development remain largely unclear. Therefore, this study aimed to investigate the effect and mechanism of montelukast on BPD in vivo and in vitro.Material/MethodsA mouse BPD model and hyperoxia-induced lung cell injury model were established and treated with montelukast. Then mean linear intercept (MLI), radial alveolar count (RAC), lung weight/body weight (LW/BW) ratio, pro-inflammatory factors, and oxidative stress-related factors in lung tissues were determined. Cell viability and apoptosis were detected using MTT assay and flow cytometer respectively.ResultsThe results showed that montelukast treatment relieved mouse BPD, evidenced by increased RAC and decreased MLI and LW/BW ratios. We also found that montelukast treatment reduced pro-inflammatory factors (TNF-α, IL-6, and IL-1β) production, enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) content in the lung tissues of BPD mice. Besides, montelukast eliminated the reduced cell viability and enhanced cell apoptosis induced by hyperoxia exposure in vitro. Moreover, the upregulated pro-inflammatory factors production and p-p65 protein level in lung cells caused by hyperoxia were decreased by montelukast treatment.ConclusionsMontelukast protected against mouse BPD induced by hyperoxia through inhibiting inflammation, oxidative stress, and lung cell apoptosis.

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Section: Introductionmentioning

confidence: 99%

Effect of Montelukast on Bronchopulmonary Dysplasia (BPD) and Related Mechanisms

2019

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“…Montelukast, a potent antagonist of the CysLT 1 receptor, exerts anti-inflammatory effects by inhibiting activation of NF-κB and secretion of IL-6 and IL-8. 47 In mice with CIA, montelukast treatment reduced both the disease incidence and its activity. 48,49 This result suggests that CysLT 1 receptor antagonism may be a promising novel therapeutic approach to reducing inflammation and disease severity in RA patients.…”

Section: Classification Of Lts and Their Targeted Therapy In Ramentioning

confidence: 99%

The roles of small‐molecule inflammatory mediators in rheumatoid arthritis

Cheng

2020

Scand J Immunol

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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by chronic and invasive inflammation and the progressive destruction of cartilage and bone. Cytokines and other inflammatory mediators are known to play important roles in the persistence of synovial inflammation, which is an essential feature of RA. Biological drugs targeting inflammatory cytokines such as TNF-α, IL-6 and IL-1 are becoming increasingly significant components of treatment regimens for RA, and monotherapy and combination therapy with synthetic disease-modifying anti-rheumatic drugs have shown excellent efficacy in many patients. 1,2 However, approximately 30% of patients with RA fail to achieve remission after treatment with these biological drugs. 3,4 Therefore, understanding the pathways that promote and reduce inflammation is an important priority for the development of novel therapies for RA. Small-molecule inflammatory mediators are defined as secreted chemical messengers that act on immune and vascular cells to contribute to the inflammatory response. 5 These molecules include lipid derivatives such as prostaglandins (PGs), leukotrienes (LTs), lipoxins (LXs) and platelet-activating factor (PAF); and components of the redox system such as reactive oxygen species (ROS) and nitric oxide (NO), among other related compounds. The mediators play a vital role not only in the development of RA but also in its progression. PGs have both pro-and anti-inflammatory effects, and some progress has been made in the treatment of RA with selective agonists of PG receptors. 6 LTs generally have pro-inflammatory properties, 7 whereas ROS regulate signal transduction. Notably, a strong positive correlation has been

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“…Montelukast was from MedChemExpress, Princeton, NJ, USA and dissolved in dimethyl sulfoxide. To determine the effects of montelukast on PGC-1a expression, cells were stimulated with montelukast (5, 10 and 20 mM) [11,12] for 24 h in 6-well plates. To determine the effects of montelukast in NRF1 and TFAM, cells were stimulated with montelukast (10 mM) for 24 h.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Montelukast promotes mitochondrial biogenesis via CREB/PGC-1α in human bronchial epithelial cells

Wang

Cheng

Liu

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Bronchial epithelial mitochondrial dysfunction including impaired mitochondrial biogenesis has been linked with the initiation and development of bronchial asthma. Montelukast, a robust antagonist of cysteinyl leukotriene receptors, has been widely applied for the therapies of bronchial asthma. However, the effects of montelukast in airway epithelial mitochondrial dysfunction are less reported. In the present study, we report that montelukast treatment in human bronchial epithelial cells of Beas-2b increased the expressions of PGC-1a, NRF-1 and TFAM. As expected, montelukast promoted mitochondrial biogenesis in Beas-2b cells through increasing mitochondrial mass, mtDNA/nDNA and the expression of cytochrome B. Importantly, we found that montelukast caused a functional gain in mitochondria of Beas-2b cells. Mechanistically, we found that montelukast treatment increased intracellular cAMP levels and activation of CREB. Blockage of CREB with H89 abolished montelukast-induced expression of PGC-1a. These findings report a novel pharmacological function of montelukast in stimulating mitochondrial biogenesis in Beas-2b cells, mediating by the CREB/PGC-1a pathway.

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Montelukast inhibits inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes

Cited by 21 publications

References 35 publications

Effect of Montelukast on Bronchopulmonary Dysplasia (BPD) and Related Mechanisms

Effect of Montelukast on Bronchopulmonary Dysplasia (BPD) and Related Mechanisms

The roles of small‐molecule inflammatory mediators in rheumatoid arthritis

Montelukast promotes mitochondrial biogenesis via CREB/PGC-1α in human bronchial epithelial cells

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