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Home / Equine Research Bank / BMC Vet Res / Non-genomic action of beclomethasone dipropionate on broncho...
BMC veterinary research2012; 8; 160; doi: 10.1186/1746-6148-8-160

Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse.

Abstract: Glucocorticoids have been proven to be effective in the therapy of recurrent airway obstruction (RAO) in horses via systemic as well as local (inhalative) administration. Elective analysis of the effects of this drug on bronchoconstriction in viable lung tissue offers an insight into the mechanism of action of the inflammatory cascade occurring during RAO which is still unclear. The mechanism of action of steroids in treatment of RAO is thought to be induced through classical genomic pathways. We aimed at electively studying the effects of the glucocorticoid beclomethasone dipropionate on equine precision-cut lung slices (PCLS).PCLS were used to analyze ex-vivo effects of beclomethasone on inhibiting bronchoconstriction in the horse. The inhibiting effect was measured through instillation of a known mediator of inflammation and bronchoconstriction, leukotriene C4. For this, the accessory lobes of 13 horses subjected to euthanasia for reasons unrelated to the respiratory apparatus were used to obtain viable lung slices. Results: After 30 minutes of PCLS incubation, beclomethasone showed to significantly inhibit the contraction of the bronchioles after instillation with leukotriene C4. The EC50 values of the two contraction curves (LTC4 with and without BDP) differed significantly from each other (p = 0.002). The possibility of a non-genomic rapid mechanism of action seems likely since transcriptional activities require a longer lag period. Conclusions: In human neuroendocrinology, high levels of glucocorticoids have been proven to function via a non-genomic mechanism of membrane receptors. The concentration of beclomethasone used on the lung slices in our study can be considered as high. This allows speculation about similar rapid non-genomic mechanisms of high-dosage inhaled glucocorticoids in the lower airways of horses. However, further assessment on a molecular basis is needed to confirm this.
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Publication Date: 2012-09-10 PubMed ID: 22963524PubMed Central: PMC3485115DOI: 10.1186/1746-6148-8-160Google Scholar: Lookup
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  • Journal Article
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article presents findings on the non-genomic action of beclomethasone dipropionate, a glucocorticoid, in reducing bronchoconstriction caused by leukotriene C4 on cut lung slices of horses. It hints at a possible rapid non-genomic response mechanism that glucocorticoids may involve in treating recurrent airway obstruction in horses.

Objective of the Research

  • The objective of this study was to examine the effects of the glucocorticoid beclomethasone dipropionate on bronchoconstriction in the lungs of horses. The aim was to gain more understanding of how glucocorticoids, proven effective in treating airway obstruction in horses, work to reduce inflammation and bronchoconstriction.

Methodology

  • Scientists used precision-cut lung slices (PCLS) from horses to analyse the action of beclomethasone. Horses used for the study were not subjected to euthanasia due to respiratory-related illnesses.
  • The lung slices were exposed to Leukotriene C4, a known mediator of inflammation and bronchoconstriction.
  • The contraction of the bronchioles in the lung slices in response to Leukotriene C4, with and without the presence of beclomethasone, were studied and compared.

Findings

  • The results of the research showed that after 30 minutes of incubation in PCLS, beclomethasone significantly reduced the contraction of bronchioles instilled with leukotriene C4.
  • The half maximal effective concentration (EC50) values of contractions induced by leukotriene C4, with and without beclomethasone, differed significantly.
  • This significant difference in effect and the rapid response of beclomethasone suggests a likely non-genomic mechanism at play. Non-genomic mechanisms involve faster cellular responses as compared to nuclear-targeted, or genomic, responses that involve transcriptional activities and require a longer time.

Implications and Conclusions

  • In human neuroendocrinology, high levels of glucocorticoids have been associated with non-genomic mechanisms, suggesting similar possibilities in horses.
  • The use of a high concentration of beclomethasone on lung slices in the study also hints at such non-genomic mechanisms in the lower airways of horses when treated with high-dose inhaled glucocorticoids.
  • However, further research is needed to confirm this suspected non-genomic mechanism of glucocorticoids at a molecular level.

Cite This Article

APA
Fugazzola M, Barton AK, Niedorf F, Kietzmann M, Ohnesorge B. (2012). Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse. BMC Vet Res, 8, 160. https://doi.org/10.1186/1746-6148-8-160

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 8
Pages: 160

Researcher Affiliations

Fugazzola, Maria
  • University of Veterinary Sciences Hanover, Clinic for Horses, Hanover, Germany. maria.fugazzola@gmail.com
Barton, Ann-Kristin
    Niedorf, Frank
      Kietzmann, Manfred
        Ohnesorge, Bernhard

          MeSH Terms

          • Animals
          • Anti-Asthmatic Agents / pharmacology
          • Beclomethasone / pharmacology
          • Bronchoconstriction / drug effects
          • Female
          • Horses
          • Leukotriene C4 / pharmacology
          • Lung / drug effects
          • Lung / physiology
          • Male

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          Citations

          This article has been cited 3 times.
          1. Michalaki C, Dean C, Johansson C. The Use of Precision-Cut Lung Slices for Studying Innate Immunity to Viral Infections. Curr Protoc 2022 Aug;2(8):e505.
            doi: 10.1002/cpz1.505pubmed: 35938685google scholar: lookup
          2. Mainguy-Seers S, Lavoie JP. Glucocorticoid treatment in horses with asthma: A narrative review. J Vet Intern Med 2021 Jul;35(4):2045-2057.
            doi: 10.1111/jvim.16189pubmed: 34085342google scholar: lookup
          3. Liu G, Betts C, Cunoosamy DM, Åberg PM, Hornberg JJ, Sivars KB, Cohen TS. Use of precision cut lung slices as a translational model for the study of lung biology. Respir Res 2019 Jul 19;20(1):162.
            doi: 10.1186/s12931-019-1131-xpubmed: 31324219google scholar: lookup
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