文献类型： 外文期刊

作者： Mei, Xiuzhen ¹ ; Wang, Jian ² ; Zhang, Chao ³ ; Zhu, Jiale ³ ; Liu, Beibei ² ; Xie, Qingyun ² ; Yuan, Ting ² ; Wu, Yuzi ² ; Chen, Rong ² ; Xie, Xing ² ; Wei, Yanna ² ; Wang, Li ² ; Shao, Guoqing ² ; Xiong, Qiyan ² ; Xu, Yefen ⁴ ; Feng, Zhixin ¹ ; Zhang, Zhenzhen ¹ ;

作者机构： 1.Nanjing Agr Univ, Coll Vet Med, Nanjing, Peoples R China

2.Jiangsu Acad Agr Sci, Inst Vet Med, Nanjing, Peoples R China

3.China Pharmaceut Univ, Sch Tradit Chinese Pharm, Nanjing, Peoples R China

4.Tibet Agr & Anim Husb Coll, Dept Anim Sci, Linzhi, Peoples R China

5.100, Linzhi 860000, Peoples R China

6.Zhongling St 50, Nanjing 21004, Jiangsu, Peoples R China

关键词： Apigenin; Mycoplasma pneumonia; Necroptosis; Alveolar macrophages

期刊名称：PHYTOMEDICINE （ 影响因子：7.9； 五年影响因子：6.8 ）

ISSN： 0944-7113

年卷期： 2023 年 108 卷

页码：

收录情况： SCI

摘要： Background: Mycoplasma-associated pneumonia is characterized by severe lung inflammation and immunological dysfunction. However, current anti-mycoplasma agents used in clinical practice do not prevent dysfunction of alveolar macrophages caused by the high level of the cytokine tumor necrosis factor-alpha (TNF-alpha) after mycoplasma infection. Apigenin inhibits the production of TNF-alpha in variet inflammation associated disease. Purpose: This study aimed to investigate apigenin's effect on mycoplasma-induced alveolar immune cell injury and the mechanism by which it inhibits TNF-alpha transcription. Methods: In this study, we performed a mouse model of Mycoplasma hyopneumoniae infection to evaluate the effect of apigenin on reducing mycoplasma-induced alveolar immune cell injury. Furthermore, we carried out transcriptome analysis, RNA interference assay, methylated DNA bisulfite sequencing assay, and chromatin immunoprecipitation assay to explore the mechanism of action for apigenin in reducing TNF-alpha. Results: We discovered that M. hyopneumoniae infection-induced necroptosis in alveolar macrophages MH-S cells and primary mouse alveolar macrophages, which was activated by TNF-alpha autocrine. Apigenin inhibited M. hyopneumoniae-induced elevation of TNF-alpha and necroptosis in alveolar macrophages. Apigenin inhibited TNF-a mRNA production via increasing ubiquitin-like with PHD and RING finger domains 1 (Uhrf1)-dependent DNA methylation of the TNF-a promotor. Finally, we demonstrated that apigenin regulated Uhrf1 transcription via peroxisome proliferator activated receptor gamma (PPAR gamma) activation, which acts as a transcription factor binding to the Uhrf1 promoter and protected infected mice's lungs, and promoted alveolar macrophage survival. Conclutsion: This study identified a novel mechanism of action for apigenin in reducing alveolar macrophage necroptosis via the PPAR gamma/Uhrf1/TNF-alpha pathway, which may have implications for the treatment of Mycoplasma pneumonia.