Cysteinyl Leukotriene Synthesis via Phospholipase A2 Group IV Mediates Exercise-induced Bronchoconstriction and Airway Remodeling

Ueno, Hiroshi; Koya, Toshiyuki; Takeuchi, Hiroyuki; Tsukioka, Keisuke; Saito, Akira; Kimura, Yo; Hayashi, Masachika; Watanabe, Satoshi; Hasegawa, Takashi; Arakawa, Masaaki; Kikuchi, Toshiaki

doi:10.1165/rcmb.2019-0325oc

Cited by 12 publications

(7 citation statements)

References 38 publications

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“…However, in our study, stimulation by montelukast did not significantly affect analyzed markers. Interestingly, in murine models, montelukast, unlike dexamethasone, decreased airway hyperresponsiveness [ 30 ], although, it is well-known that the combination of inhaled glucocorticoids and montelukast was proven to be beneficial in asthmatic patients [ 31 ]. However, we observed enhancement of ACTA2 expression following combined treatment with beclomethasone 17-propionate and montelukast sodium.…”

Section: Discussionmentioning

confidence: 99%

Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling?

Sobczak¹,

Pawliczak²

2022

IJMS

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Vitamin D is commonly known for its properties of airway remodeling inhibition. Due to this, we decided to analyze the action of calcitriol with anti-asthmatic drugs in airway remodeling. The HFL1 cell line was treated with calcitriol, beclomethasone 17-propionate, montelukast sodium, LTD4 and TGF-β in different combinations. Real-time PCR was used to analyzed the expression of ACTA2, CDH-1, Vimentin, ADAM33, MMP-9 and CysLTR1 on the mRNA level, whereas Western blot was used to analyze gene expression on the protein level. One-way analysis variants, the Kruskal-Wallis test, Student’s t-test or Welch’s t-test were used for statistical analysis. Concerning the results, pre-treatment with calcitriol increased the inhibitory effect of beclomethasone 17-propionate and montelukast sodium on the expression of ACTA2 (p = 0.0072), Vimentin (p = 0.0002) and CysLTR1 (p = 0.0204), and 1,25(OH)2D3 had an influence on the effects of beclomethasone 17-propionate and montelukast sodium and of CDH1 expression (p = 0.0076). On the protein level, pre-treatment with calcitriol with beclomethasone 17-propionate and montelukast sodium treatment decreased ACTA2 expression in comparison to the LT (LTD4 and TGF-β) control group (p = 0.0191). Hence, our study not only confirms that vitamin D may inhibit airway remodeling, but also shows that vitamin D has a synergistic effect with anti-asthmatic drugs.

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Section: Discussionmentioning

confidence: 99%

Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling?

Sobczak¹,

Pawliczak²

2022

IJMS

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“…106 These studies have helped elucidate contributions of airflowinduced bronchoconstriction, its stimulation by airway drying and inhibition by cooling stimuli, the resulting damage to the bronchial mucosa by hyperpnea with dry air, the role of the airway smooth muscle and airway epithelium, the biochemical mediators participating (including cysteinyl-leukotrienes and pro-inflammatory cytokines), as well as the airway and vascular responses to dehydration during EIB. [106][107][108] However, to our discernment, no studies have specifically addressed sex differences in EIB in animal models, nor assessed the roles of sex hormones EIB mechanisms.…”

Section: Sex Differences In Eibmentioning

confidence: 99%

Asthma, atopy, and exercise: Sex differences in exercise-induced bronchoconstriction

Bauza

Silveyra

2021

Exp Biol Med (Maywood)

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Asthma is a chronic inflammatory lung disease affecting approximately 7.7% of the US population. Sex differences in the prevalence, incidence, and severity of asthma have been widely described throughout the lifespan, showing higher rates in boys than girls before puberty, but a reversed pattern in adults. Asthma is often associated with atopy, i.e. the tendency to develop allergic diseases, and can be worsened by environmental stimuli and/or exercise. While not exclusive to patients with asthma, exercise-induced bronchoconstriction (EIB) is a common complication of athletes and individuals who exercise regularly. Currently, there is limited research on sex differences in EIB and its relationship with atopy and asthma in men and women. In this minireview, we summarize the available literature on this topic. Overall, the collective knowledge supports the notion that physiological changes triggered during exercise affect males and females differently, suggesting an interaction among sex, exercise, sex hormones, and atopic status in the course of EIB pathophysiology. Understanding these differences is important to provide personalized management plans to men and women who exercise regularly and suffer from underlying asthma and/or atopy.

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“…The results of modern studies demonstrate an increase in the excreted with urinary prostaglandin metabolite D2 and LT E4 after intensive physical activity. People suffering from EIB were diagnosed with a significant increase in the concentration of cysteinyl LT, histamine, and tryptase in sputum when taking physical activity [19]. Decreased level of inflammatory mediators in sputum has been found to be associated with the administration of drugs such as montelukast and loratadine [16].…”

Section: Peculiarities Of Effort-induced Bronchospasm Pathogenesis In High-school Teenagersmentioning

confidence: 99%

“…At the same time, straight after physical activity is taken, an increase in the LT V4 and LT C4 mediator concentration in the blood is observed. It has also been found that intensive physical activity is the most important factor to initiate cysteinyl LT production due to activated gene expression responsible for the 5-lipoxygenase eicosatetraenoic acid transformation pathway [19,20]. In the current literature, there is conflicting evidence regarding the role of nitric oxide (NO) in the formation of pathophysiological mechanisms for EIB development.…”

Section: Peculiarities Of Effort-induced Bronchospasm Pathogenesis In High-school Teenagersmentioning

confidence: 99%

Effort-induced bronchospasm in athletes: modern views on pathogenesis and diagnosis in high-school teenagers

Mikhailovna¹,

Chebysheva²,

Meleshkina³

et al. 2021

J Adv Pharm Educ Res

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Cysteinyl Leukotriene Synthesis via Phospholipase A2 Group IV Mediates Exercise-induced Bronchoconstriction and Airway Remodeling

Cited by 12 publications

References 38 publications

Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling?

Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling?

Asthma, atopy, and exercise: Sex differences in exercise-induced bronchoconstriction

Effort-induced bronchospasm in athletes: modern views on pathogenesis and diagnosis in high-school teenagers

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