ISSN: 1449-1907International Journal of Medical Sciences
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Int J Med Sci 2024; 21(6):1003-1015. doi:10.7150/ijms.91253 This issue Cite
Research Paper
Combination of androgen and estrogen improves asthma by mediating Runx3 expression
1. Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China.
2. Department of Emergency Medicine, The Second Xiangya Hospital, Central South University, Emergency and Difficult Diseases Institute of Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China.
3. Department of Respiratory Medicine, The Second Affiliated Hospital of Hainan Medical University, 48 Pak Shui Tong Road, Haikou, Hainan 570000, China.
4. Department of Respiratory and Critical Care Medicine, Hunan Provincial People's Hospital, 61 West Jiefang Road, Changsha, Hunan 410005, China.
5. Department of Respiratory and Critical Care Medicine, Longshan County People's Hospital, Longshan, Hunan 416800, China.
6. Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guilin Medical University, 15 Le Qun Road, Guilin, Guangxi 541001, China.
Abstract
Objective: Asthma is a chronic heterogeneous airway disease, and imbalanced T-helper type 1 (Th1) and Th2 cell-mediated inflammation contribute to its pathogenesis. Although it has been suggested that androgen and estrogen were involved in development of asthma, the underlying mechanisms remained largely unclear. Studies have demonstrated that Runx3 could promote naive CD4+ T cells to differentiate into Th1 cells. Hence, our study aimed to explore the potential regulatory mechanism of androgen and estrogen on asthma via modulating Runx3.
Methods: First, clinical assessments and pulmonary function tests were conducted on 35 asthma patients and 24 healthy controls. The concentrations of androgen, estrogen, and androgen estrogen ratios were assessed in peripheral blood samples of asthma patients and healthy controls. Then, a murine asthma model was established to explore the effects of estrogen and androgen (alone or in combination) on asthma. Third, an in vitro assay was used to explore the mechanism of combination of androgen and estrogen in asthma.
Results: We observed decreased androgen and increased estrogen levels in asthma patients compared with healthy controls. In mice with experimental asthma, there were increased serum concentrations of estrogen and decreased serum concentrations of androgen, intervention with combination of androgen and estrogen alleviated airway inflammations, increased Runx3 expressions and elevated Th1 differentiation. In CD4+ T cells co-cultured with bronchial epithelial cells (BECs), treatment with androgen plus estrogen combination promoted Th1 differentiation, which was mitigated by Runx3 knockdown in BECs and enhanced by Runx3 overexpression.
Conclusion: These findings suggest that androgen estrogen combination modulate the Th1/Th2 balance via regulating the expression of Runx3 in BECs, thereby providing experimental evidence supporting androgen and estrogen combination as a novel therapy for asthma.
Keywords: androgen, estrogen, asthma, Runx3
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