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Effects of Inhalation of STIM-Orai Antagonist SKF 96365 on Ovalbumin-Induced Airway Remodeling in Guinea Pigs

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Best Practice in Health Care

Part of the book series: Advances in Experimental Medicine and Biology ((CLEXBI,volume 1335))

Abstract

Airway remodeling (AR) consists of wall thickening and hyperreactivity. STIM (stromal interaction molecule) and Orai protein pathways mediate extracellular Ca2+ signals involved in AR. This study aims to define the effects on AR of the STIM-Orai antagonist SKF 96365 given by inhalation in three increasing doses in ovalbumin-induced AR. In the control group, the antiasthmatic budesonide and salbutamol were given in the same model. The airway structure was evaluated by histological and immunohistochemistry and reactivity by specific airway resistance, contraction strength of isolated airway smooth muscles, and mucociliary clearance expressed by ciliary beating frequency. The immuno-biochemical markers of chronic inflammation were evaluated by BioPlex and ELISA assays. The AR was mediated by inflammatory cytokines and growth factors. The findings show significant anti-remodeling effects of SKF 96365, which were associated with a decrease in airway hyperreactivity. The anti-remodeling effect of SKF 96365 was mediated via the suppression of IL-4, IL-5, and IL-13 synthesis, and IL-12–INF-γ–TGF-β pathway. The budesonide-related AR suppression had to do with a decrease in proinflammatory cytokines and an increase in the anti-inflammatory IL-10, with negligible influence on growth factors synthesis and mucous glands activity.

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Acknowledgments

We thank Ms. Katarina Jesenska for the outstanding technical assistance during the experimental work and Ms. Slavka Drahosova for immunohistochemical analyses. The study was supported by grants: VEGA 1/0314/21, VEGA 1/0253/19, APVV 19-0033, and the research project of the Biomedical Center Martin—ITMS 26220220187, entitled “We support research activities in Slovakia” cofinanced by the EU.

Conflicts of Interest

The authors declare no conflicts of interest concerning this article.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The animals were treated in accord with the Guide for the Care and Use of Laboratory Animals (8th edition, National Academies Press) and the EU and Slovakian legislation regulating the welfare of experimental animals. This study was approved by a local Ethics Committee of the Jessenius Faculty of Medicine in Martin, Slovakia (permit EK 40/2018), registered by the Institutional Review Board/Ethics Board Office.

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Authors and Affiliations

  1. Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Mala Hora, Martin, Slovakia

    Martina Šutovská, Michaela Kocmálová, Ivana Kazimierová, Christina Imnoy Nøss Forsberg, Marta Jošková & Soňa Fraňová

  2. Martin’s Biomedical Center (BioMed), Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia

    Michaela Kocmálová & Ivana Kazimierová

  3. Institute of Histology and Embryology Jessenius Faculty of Medicine Comenius University, Martin, Slovakia

    Marian Adamkov

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  1. Martina Šutovská
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Correspondence to Michaela Kocmálová .

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    Mieczyslaw Pokorski

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Šutovská, M. et al. (2021). Effects of Inhalation of STIM-Orai Antagonist SKF 96365 on Ovalbumin-Induced Airway Remodeling in Guinea Pigs. In: Pokorski, M. (eds) Best Practice in Health Care. Advances in Experimental Medicine and Biology(), vol 1335. Springer, Cham. https://doi.org/10.1007/5584_2021_633

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