Suppression of IL-8 production from airway cells by tiotropium bromide in vitro

Suzaki, Isao; Asano, Koichiro; Shikama, Yusuke; Hamasaki, Taisuke; Kanei, Ayako; Suzaki, Harumi

doi:10.2147/copd.s23695

Cited by 14 publications

(13 citation statements)

References 38 publications

(54 reference statements)

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“…However, the potential effects of antimuscarinics on structural and functional changes of bladders caused by BOO have not been explored so far. Nevertheless, recent findings implicate that muscarinic receptors are able to enhance the cell proliferation, modulate contractile protein expression and participate in the release of inflammatory cytokines [6-9]. But, up to date, the role of antimuscarinics and muscarinic receptors in bladder function and structure is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction

Liu

Luo

Yang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Overactive bladder associated with bladder outlet obstruction (BOO) is a highly prevalent condition, which is usually treated with antimuscarinics. However, the potential effects of antimuscarinics on the structure and function of bladder have not been investigated thus far. Methods: Sprague-Dawley(R) rats accepted bladder neck obstruction surgery or sham surgery, and then received treatment of three different antimuscarinics (Solifenacin, Darifenacin, and Tolterodine) or vehicle. After 3, 6 and 12 weeks, the bladder function and structure were measured. The effect of antimuscarinics on cellular alteration in vitro was observed under mechanical stimulation. Bladder morphology were examined by immunohistochemistry, and the bladder function were investigated by cystometry and strip contractility test. The expression of muscarinic receptors and inflammatory cytokines were measured by PCR and Western blotting. Results: Here we demonstrate, both in vitro and in vivo, that antimuscarinics are protective regulators for the bladder structure and function. Antimuscarinics decrease the weight of bladders with BOO. Antimuscarinics improve the voiding parameter and enhance the contraction of bladder smooth muscle. The results also show that antimuscarinics inhibit the proliferation of bladder smooth muscle cells both in vivo and in vitro, it can reduce the collagen deposition and inflammatory cytokines in bladders with BOO. During this process, the expression of M2 and M3 receptors was altered by antimuscarinics. Conclusion: Antimuscarinics could reverse the structural and functional changes of BOO bladder wall at cellular and tissue level, and the alteration of M2 and M3 receptors may be involved in this biological process.

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Section: Introductionmentioning

confidence: 99%

Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction

Liu

Luo

Yang

et al. 2017

Cell Physiol Biochem

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“…Furthermore, tiotropium reduced inflammation and remodeling in several models of asthma ( Gosens et al, 2005 ; Bos et al, 2007 ; Ohta et al, 2010 ; Buels et al, 2012 ; Bosnjak et al, 2014 ). In addition, several in vitro studies also attest to the anti-inflammatory properties of tiotropium ( Buhling et al, 2007 ; Asano et al, 2008 ; Bateman, et al, 2009 ; Suzaki, et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Tiotropium Attenuates Virus-Induced Pulmonary Inflammation in Cigarette Smoke-Exposed Mice

Bucher

Duechs

Tilp

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Viral infections trigger exacerbations in chronic obstructive pulmonary disease (COPD), and tiotropium, a M3 receptor antagonist, reduces exacerbations in patients by unknown mechanisms. In this report, we investigated whether tiotropium has anti-inflammatory effects in mice exposed to cigarette smoke (CS) and infected with influenza virus A/PR/8/34 (H1N1) or respiratory syncytial virus (RSV) and compared these effects with those of steroid fluticasone and PDE4-inhibitor roflumilast. Mice were exposed to CS; infected with H1N1 or RSV; and treated with tiotropium, fluticasone, or roflumilast. The amount of cells and cytokine levels in the airways, lung function, and viral load was determined. NCI-H292 cells were infected with H1N1 or RSV and treated with the drugs. In CS/H1N1-exposed mice, tiotropium reduced neutrophil and macrophage numbers and levels of interleukin-6 (IL-6) and interferon-γ (IFN-γ) in the airways and improved lung function. In contrast, fluticasone increased the loss of body weight; failed to reduce neutrophil or macrophage numbers; increased IL-6, KC, and tumor necrosis factor-α (TNF-α) in the lungs; and worsened lung function. Treatment with roflumilast reduced macrophage numbers, IL-6, and KC in the lungs but had no effect on neutrophil numbers or lung function. In CS/RSV-exposed mice, treatment with tiotropium, but not fluticasone or roflumilast, reduced neutrophil numbers and IL-6 and TNF-α levels in the lungs. Viral load of H1N1 and RSV was significantly elevated in CS/virus-exposed mice and NCI-H292 cells after fluticasone treatment, whereas tiotropium and roflumilast had no effect. In conclusion, tiotropium has anti-inflammatory effects on CS/virus-induced inflammation in mice that are superior to the effects of roflumilast and fluticasone. This finding might help to explain the observed reduction of exacerbation rates in COPD patients.

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“…In several animal models tiotropium has been found to attenuate acute and chronic pulmonary inflammation [ 30 – 32 ]. Several studies in vitro also showed that tiotropium could suppress LPS-induced the release of neutrophil chemotactic mediators by human airway epithelial cells, lung fibroblasts and alveolar macrophages [ 5 , 6 ]. Together with the finding showing inhibitory effect of tiotropium on Cd-induced inflammatory changes in the present model, including a significant decrease of neutrophils and protein concentration in BALF accompanied with a marked attenuation of extent and severity of acute pulmonary inflammatory infiltration, we suggest that the decrease of airway hyperresponsiveness might be related to the anti-inflammatory mechanisms of tiotropium.…”

Section: Discussionmentioning

confidence: 99%

“…The anti-inflammatory effect of long-acting muscarinic antagonists (LAMAs) has been mentioned by several studies in vitro and in vivo [ 4 – 6 ]. Tiotropium has been reported to have an anti-inflammatory activity on cigarette smoke induced pulmonary inflammation in mice [ 4 ] and can inhibit cytokines production from structural and inflammatory cells [ 5 – 6 ]. However, whether tiotropium could reduce the severity and frequency of AECOPD by inhibiting neutrophilic infiltration remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats

Zhao

Yang

et al. 2018

PLoS ONE

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As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70μg/15ml or 350μg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70μg/15ml) or budesonide (250μg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness.

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Suppression of IL-8 production from airway cells by tiotropium bromide in vitro

Cited by 14 publications

References 38 publications

Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction

Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction

Tiotropium Attenuates Virus-Induced Pulmonary Inflammation in Cigarette Smoke-Exposed Mice

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats

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