Inhibition of p38 MAPK-dependent bronchial contraction after ozone by corticosteroids

Li, Feng; Zhang, M.; Hussain, Faheem; Triantaphyllopoulos, Kostas A.; Clark, Andrew R.; Bhavsar, PK; Zhou, Xin; Chung, Kian Fan

doi:10.1183/09031936.00021110

Cited by 35 publications

(33 citation statements)

References 36 publications

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“…In order to understand how IL-17 can modulate the contractile process, we studied the contractile responses of the intrapulmonary airways in the presence of a selective p38 MAPK inhibitor, SB239063 (10 −6 M), and of a corticosteroid, dexamethasone (10 −6 M), as previously described [14]. In the presence of SB239063, there was a reduction in the maximal contractility response in both mouse strains exposed to air or to ozone.…”

Section: Resultsmentioning

confidence: 99%

“…IL-17 has also been shown to activate many common downstream signalling pathways, including NF-κB, and the MAPKs (mitogen-activated protein kinases) JNK (c-Jun N-terminal kinase), p38 and ERK (extracellular-signal-regulated kinase), together with other kinases including PI3K (phosphoinositide 3-kinase) and JAK (Janus kinase)/STATs [7]. IL-17 may increase AHR e through a direct action on the airway smooth muscle as IL-17 has been shown to activate p38 MAPK pathway in these cells [18] We have previously shown the p38 MAPK/HSP27 is involved in the ex-vivo cholinergic agonist-induced increase in bronchial smooth muscle contractility following a single exposure to ozone [14]. We now show a similar response in the airways from mice chronically-exposed to ozone, with the development of concomitant emphysema.…”

Section: Discussionmentioning

confidence: 99%

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IL-17A Modulates Oxidant Stress-Induced Airway Hyperresponsiveness but Not Emphysema

Pinart

Zhang

et al. 2013

PLoS ONE

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IL-17A induces the release of pro-inflammatory cytokines and of reactive oxygen species which could lead to neutrophilic inflammation. We determined the role of IL-17 receptor (IL-17R) signalling in oxidant-induced lung emphysema and airway hyperresponsiveness. IL-17R−/− and wild-type C57/BL6 mice were exposed to ozone (3 ppm; 3 hours) for 12 times over 6 weeks. Bronchial responsiveness to acetylcholine was measured, and lungs were retrieved. Mean linear intercept (Lm) and isometric contractile responses of intrapulmonary airways to acetylcholine were determined. In wild-type mice but not in IL-17R−/−, chronic ozone exposure caused airway hyperresponsiveness. The increase in Lm after chronic ozone exposure of wild-type mice was also observed in IL-17R−/− mice. The increased maximal contractile response to acetylcholine seen in airways of wild-type mice exposed to ozone was abolished in IL-17R−/− mice. p38-mitogen-activated protein kinase (MAPK) and dexamethasone-dependent increase in contractile response was reduced in airways from IL-17R−/− ozone-exposed mice. Lung inflammation scores were not altered in IL-17R−/− mice exposed to ozone compared to wild-type mice. The increased release of IL-17 and IL-1β, and the activation of p38 MAPK in the lungs of ozone-exposed mice was reduced in IL-17R−/− mice. IL-17R signalling underlies the increase in airway hyperresponsiveness seen after ozone exposure, mediated by the increased contractility of airway smooth muscle. The emphysema and lung inflammation induced by ozone is not dependent on IL-17.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

IL-17A Modulates Oxidant Stress-Induced Airway Hyperresponsiveness but Not Emphysema

Pinart

Zhang

et al. 2013

PLoS ONE

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“…The mechanisms involved in this phenomenon include an increase in pro-inflammatory mediators (kinins and interleukins) (37), oxidant lipid mediators (38) and nitric oxide (39). It is noteworthy these mechanisms were mostly studied using only indirect methods such as questionnaires and measurement of gases.…”

Section: Discussionmentioning

confidence: 99%

Intensity of swimming exercise influences tracheal reactivity in rats

Brito

Silva

Souza

et al. 2015

J. Smooth Muscle Res.

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Studies that evaluate the mechanisms for increased airway responsiveness are very sparse, although there are reports of exercise-induced bronchospasm. Therefore, we have evaluated the tracheal reactivity and the rate of lipid peroxidation after different intensities of swimming exercise in rats. Thus, male Wistar rats (age 8 weeks; 250–300 g) underwent a forced swimming exercise for 1 h whilst carrying attached loads of 3, 4, 5, 6 and 8% of their body weight (groups G3, G4, G5, G6 and G8, respectively; n=5 each). Immediately after the test, the trachea of each rat was removed and suspended in an organ bath to evaluate contractile and relaxant responses. The rate of lipid peroxidation was estimated by measuring malondialdehyde levels. According to a one-way ANOVA, all trained groups showed a significant decrease in the relaxation induced by aminophylline (10−12–10−1 M) (pD2=3.1, 3.2, 3.3, 3.3 and 3.2, respectively for G3, G4, G5, G6 and G8) compared to the control group (pD2=4.6) and the Emax values of G5, G6, G8 groups were reduced by 94.2, 88.0 and 77.0%, respectively. Additionally, all trained groups showed a significant increase in contraction induced by carbachol (10−9–10−3 M) (pD2=6.0, 6.5, 6.5, 7.2 and 7.3, respectively for G3, G4, G5, G6 and G8) compared to the control group (pD2=5.7). Lipid peroxidation levels of G3, G4 and G5 were similar in both the trachea and lung, however G6 and G8 presented an increased peroxidation in the trachea. In conclusion, a single bout of swimming exercise acutely altered tracheal responsiveness in an intensity-related manner and the elevation in lipid peroxidation indicates a degree of oxidative stress involvement.

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“…Corticosteroids can inhibit the activity of p38 MAPK by upregulating the expression of MKP‐1 in airway smooth muscle . In addition, p38 MAPK activation has been implicated as a mechanism of corticosteroid insensitivity in severe asthma …”

Section: Introductionmentioning

confidence: 99%

Activation of p38 mitogen‐activated protein kinase in ovalbumin and ozone‐induced mouse model of asthma

Bao

et al. 2013

Respirology

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Background and objective: Ozone exposure worsens the development of allergen-induced asthma. The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in the development of the inflammatory response, airway hyperresponsiveness (AHR) and airway remodelling. In this study, the role of the p38 MAPK pathway on the effects of chronic ozone exposure in ovalbumin (OVA)-sensitized and -challenged mice was investigated. Methods: Mice were sensitized and challenged with OVA followed by ozone exposure. Dexamethasone (Dex) and SB239063, a p38 MAPK inhibitor, were used as preventive treatment.

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Inhibition of p38 MAPK-dependent bronchial contraction after ozone by corticosteroids

Cited by 35 publications

References 36 publications

IL-17A Modulates Oxidant Stress-Induced Airway Hyperresponsiveness but Not Emphysema

IL-17A Modulates Oxidant Stress-Induced Airway Hyperresponsiveness but Not Emphysema

Intensity of swimming exercise influences tracheal reactivity in rats

Activation of p38 mitogen‐activated protein kinase in ovalbumin and ozone‐induced mouse model of asthma

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