The Role of Inosine Monophosphate Dehydrogenase in Ovalbumin-induced Allergic Asthma
10.3870/j.issn.1672-0741.24.05.005
- VernacularTitle:肌苷单磷酸脱氢酶在卵清蛋白诱导过敏性哮喘中的作用
- Author:
Bimin SANG
1
;
Chunxue KONG
;
Jinglei CAO
Author Information
1. 武汉科技大学公共卫生学院,职业危害识别与控制湖北省重点实验室,环境毒理学研究室,武汉 430065
- Keywords:
inosine monophosphate dehydrogenase;
allergic asthma;
airway inflammation;
lymphocytes;
ribavirin
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2024;53(5):578-585
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of inosine monophosphate dehydrogenase(IMPDH)in the development of ovalbumin(OVA)-induced allergic asthma.Methods Thirty-six BALB/c female mice were randomly divided into a healthy con-trol group,an OVA asthma group,and an IMPDH inhibitor(ribavirin)intervention group,with 12 mice in each group.The bron-choalveolar lavage fluid(BALF),lung,peripheral blood and spleen were collected from each mouse.HE staining was used to an-alyze the pathological changes in the lung tissue,and immunohistochemistry was used to detect the expression of CD3 in the lung tissue.A hemocyte analyzer was used to determine the total number and classified counts of leukocytes in the BALF and peripheral blood.RT-PCR and Western blotting were used to detect IMPDH mRNA and protein levels,respectively,in the lung tissue.Immunofluorescence was used to detect IMPDH protein localization and expression in lung tissue,and flow cytometry was used to analyze lymphocyte subpopulations and their intracellular IMPDH protein levels in peripheral blood and spleen tis-sue.Results Compared with those in the healthy control group,the number of inflammatory cells around small airways and in alveolar spaces in the lungs of the OVA asthma group was greater,and the total number of leukocytes in both the BALF and pe-ripheral blood was significantly higher,with significant increases in the numbers of neutrophils,eosinophils,and monocytes(P＜0.05).There was also a significant increase in the level of IMPDH protein in lung tissue(P＜0.05),and immunostaining re-vealed increased expression of IMPDH protein in the cytoplasm of inflammatory cells in a dispersed pattern.Subsequently,lung inflammation was significantly reduced in OVA-induced asthmatic mice after ribavirin intervention,as characterized specifically by a significant reduction in eosinophils and neutrophils in the BALF(P＜0.05)and a decrease in the level of IMPDH protein in the lungs(P＜0.05).Furthermore,there was also a decrease in the expression of IMPDH in the cytoplasm of inflammatory cells,whereas an increased number of IMPDH-positive filamentous structures were observed in the nuclei of inflammatory cells.Additionally,the percentage of B cells in the spleens of the mice in the OVA asthma group was significantly greater than that in the control group(P＜0.05).After ribavirin intervention,the percentage of B cells in the spleens of asthmatic mice significantly decreased,whereas the percentages of NK,CD3+and CD8+T cells significantly increased(P＜0.05).Moreover,the IMPDH protein levels in NK cells increased,whereas the IMPDH protein levels in CD8+T cells decreased in the spleen.Conclusion Inhibition of IMPDH can effectively alleviate airway and systemic inflammation dominated by eosinophils.Moreover,it can also reduce the immune response of B cells and enhance the immune response effect of killer cells,such as NK and CD8 T cells,in the spleen.The underlying mechanism may be related to the level of IMPDH expression in inflammatory cells and the formation of filamentous structures.
