Monensin Suppresses Multiple Features of House Dust Mite-Induced Experimental Asthma in Mice

Overview

Journal Inflammation

Specialties Allergy & Immunology
Pathology

Date 2024 Jul 3

PMID 38958812

Authors

Venkata Sita Rama Raju Allam

Srinivas Akula

Ida Waern

Sowsan Taha

Sara Wernersson

Gunnar Pejler

Affiliations

Soon will be listed here.

Abstract

Despite intense efforts to develop efficient therapeutic regimes for asthma, there is a large demand for novel treatment strategies in this disease. Here we evaluated the impact of monensin, a drug with potent anti-mast cell effects, in a mouse model of asthma. Allergic airway inflammation was induced by sensitization of mice with house dust mite (HDM) antigen, and effects of monensin on airway hyperreactivity and inflammatory parameters were studied. Following intraperitoneal administration, monensin did not suppress airway hyperreactivity but was shown to have anti-inflammatory properties, as manifested by reduced eosinophil- and lymphocyte infiltration into the airway lumen, and by suppressed inflammation of the lung tissue. After intranasal instillation, monensin exhibited similar anti-inflammatory effects as seen after intraperitoneal administration. Moreover, intranasally administered monensin was demonstrated to suppress goblet cell hyperplasia, and to cause a reduction in the expression of genes coding for key inflammatory markers. Further, monensin blocked mast cell degranulation in the airways of allergen-sensitized mice. Together, this study reveals that monensin has the capacity to suppress key pathological events associated with allergic airway inflammation.

References

Fahy J . Type 2 inflammation in asthma--present in most, absent in many. Nat Rev Immunol. 2014; 15(1):57-65. PMC: 4390063. DOI: 10.1038/nri3786. View

Xiong D, Martin J, Lauzon A . Airway smooth muscle function in asthma. Front Physiol. 2022; 13:993406. PMC: 9581182. DOI: 10.3389/fphys.2022.993406. View

Gillissen A, Paparoupa M . Inflammation and infections in asthma. Clin Respir J. 2014; 9(3):257-69. PMC: 7162380. DOI: 10.1111/crj.12135. View

Busse W . The relationship of airway hyperresponsiveness and airway inflammation: Airway hyperresponsiveness in asthma: its measurement and clinical significance. Chest. 2010; 138(2 Suppl):4S-10S. PMC: 2914527. DOI: 10.1378/chest.10-0100. View

Holgate S, Wenzel S, Postma D, Weiss S, Renz H, Sly P . Asthma. Nat Rev Dis Primers. 2016; 1:15025. PMC: 7096989. DOI: 10.1038/nrdp.2015.25. View

Lommatzsch M, Brusselle G, Levy M, Canonica G, Pavord I, Schatz M . ABCD: a concise guide for asthma management. Lancet Respir Med. 2023; 11(6):573-576. DOI: 10.1016/S2213-2600(22)00490-8. View

Andersson C, Tufvesson E, Diamant Z, Bjermer L . Revisiting the role of the mast cell in asthma. Curr Opin Pulm Med. 2015; 22(1):10-7. DOI: 10.1097/MCP.0000000000000228. View

Yu M, Tsai M, Tam S, Jones C, Zehnder J, Galli S . Mast cells can promote the development of multiple features of chronic asthma in mice. J Clin Invest. 2006; 116(6):1633-41. PMC: 1462940. DOI: 10.1172/JCI25702. View

Bradding P, Walls A, Holgate S . The role of the mast cell in the pathophysiology of asthma. J Allergy Clin Immunol. 2006; 117(6):1277-84. DOI: 10.1016/j.jaci.2006.02.039. View

10.

Brightling C, Bradding P, Symon F, Holgate S, Wardlaw A, Pavord I . Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med. 2002; 346(22):1699-705. DOI: 10.1056/NEJMoa012705. View

11.

Mendez-Enriquez E, Hallgren J . Mast Cells and Their Progenitors in Allergic Asthma. Front Immunol. 2019; 10:821. PMC: 6548814. DOI: 10.3389/fimmu.2019.00821. View

12.

Wernersson S, Pejler G . Mast cell secretory granules: armed for battle. Nat Rev Immunol. 2014; 14(7):478-94. DOI: 10.1038/nri3690. View

13.

Galli S, Nakae S, Tsai M . Mast cells in the development of adaptive immune responses. Nat Immunol. 2005; 6(2):135-42. DOI: 10.1038/ni1158. View

14.

Paivandy A, Pejler G . Novel Strategies to Target Mast Cells in Disease. J Innate Immun. 2021; 13(3):131-147. PMC: 8138242. DOI: 10.1159/000513582. View

15.

Harvima I, Levi-Schaffer F, Draber P, Friedman S, Polakovicova I, Gibbs B . Molecular targets on mast cells and basophils for novel therapies. J Allergy Clin Immunol. 2014; 134(3):530-44. DOI: 10.1016/j.jaci.2014.03.007. View

16.

Jones L, Bunnage M . Applications of chemogenomic library screening in drug discovery. Nat Rev Drug Discov. 2017; 16(4):285-296. DOI: 10.1038/nrd.2016.244. View

17.

Maccarana M, Liu J, Lampinen M, Rollman O, Adner M, Pejler G . Monensin induces selective mast cell apoptosis through a secretory granule-mediated pathway. Allergy. 2021; 77(3):1025-1028. DOI: 10.1111/all.15157. View

18.

Rama Raju Allam V, Waern I, Taha S, Akula S, Wernersson S, Pejler G . Nafamostat has anti-asthmatic effects associated with suppressed pro-inflammatory gene expression, eosinophil infiltration and airway hyperreactivity. Front Immunol. 2023; 14:1136780. PMC: 10160450. DOI: 10.3389/fimmu.2023.1136780. View

19.

Takeda K . Measurement of Airway Hyperresponsiveness in Mice. Methods Mol Biol. 2022; 2506:95-109. DOI: 10.1007/978-1-0716-2364-0_7. View

20.

Waern I, Jonasson S, Hjoberg J, Bucht A, Abrink M, Pejler G . Mouse mast cell protease 4 is the major chymase in murine airways and has a protective role in allergic airway inflammation. J Immunol. 2009; 183(10):6369-76. DOI: 10.4049/jimmunol.0900180. View