Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

MAPK1 knockdown ameliorated immune and inflammatory abnormalities in a mouse model of refractory asthma

Shuang Lin¹, Xiaohong Yang²

¹Xinjiang Medical University, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000, Xinjiang Uygur Autonomous Region, China; ²Department of Respiratory and Critical Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000, Xinjiang Uygur Autonomous Region, China.

For correspondence:- Xiaohong Yang Email: baoxianmei08436123@163.com

Accepted: 31 August 2023 Published: 30 September 2023

Citation: Lin S, Yang X. MAPK1 knockdown ameliorated immune and inflammatory abnormalities in a mouse model of refractory asthma. Trop J Pharm Res 2023; 22(9):1831-1840 doi: 10.4314/tjpr.v22i9.9

© 2023 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To evaluate the potential molecular mechanisms involved in refractory asthma in an animal model, and the potential therapeutic effect of MAPK1 knockdown on the disease.

Methods: Eighteen female Institute of Cancer Research (ICR) mice, aged 8 - 10 weeks, were randomly divided into three groups: control, asthma model and refractory asthma, with 6 mice in each group. The expression of MAPK1 was knocked down in mice using an adenoviral vector. Subsequently, the methylation levels of MAPK1 promoter in mouse lung tissue were determined using methylation assays. Hematoxylin and eosin (H&E) staining and Periodic Acid-Schiff (PAS) staining were used to determine inflammatory and histological changes in lung tissues. Levels of immune cells were determined using flow cytometry, while Western blotting was used to measure the protein expression levels of ERK1/2, JNK, MEK1/2 and p38.

Results: Methylation assay results show that mean methylation level of cg11335969 locus was significantly reduced in the refractory asthma mouse model (p < 0.05). The levels of IgG1 and IgM in refractory asthmatic mice were reduced after MAPK1 knockdown. There was a significantly reduced degree of lung lesions in mice (p < 0.05), as was reflected in effectively decreased histopathological changes. Protein levels of ERK1/2, JNK, MEK1/2 and p38, and the levels of neutrophils, dendritic cells, and macrophages were significantly decreased (p < 0.05).

Conclusion: There is hypermethylated modification of MAPK1 at cg11335969 site in refractory asthma mouse model. Knockdown of MAPK1 attenuates inflammation and tissue damage, and reverses abnormal immune cell numbers in refractory asthma mice. Thus, MAPK1 inhibition may be a novel strategy for ameliorating immune abnormalities in refractory asthma.

Keywords: Refractory asthma, MAPK1, Mouse model, Immune, Inflammatory response