文献类型：期刊文献

英文题名：Formaldehyde exacerbates asthma in mice through the potentiation of HIF-1α-mediated pro-inflammatory responses in pulmonary macrophages

作者：Ma, Huijuan[1,2];Shu, Qi[1,2];Wang, Peiyao[1,2];Qin, Ruilin[1,2];Li, Sijia[1,2];Xu, Huan[1,2]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Sch Pharm, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2023

卷号：379

外文期刊名：CHEMICO-BIOLOGICAL INTERACTIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000991408900001)】；

基金：This work was funded by National Natural Science Foundation of China [grant No. 42177417] . This work was also funded by Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission) .

语种：英文

外文关键词：Formaldehyde; Asthma; Macrophage; Glycolysis; Pro-inflammatory responses; HIF-1 alpha

摘要：Exposure to formaldehyde (FA) has been indicated to be positively correlated with increased incidence of allergic asthma in many epidemiological and experimental studies. However, few studies have ever addressed the molecular basis of the correlation. In the present study, it was found that inhaling 2.0 mg/m(3) FA for 2 weeks could exacerbate the pulmonary inflammation and mucus over-accumulation in OVA-induced murine asthmatic model. The pro-inflammatory cytokines, such as IL-1 beta, TNF-alpha, IL-6 and IL-8, were increased in lung and serum of FA-exposed asthmatic mice. The contribution of HIF-1 alpha signaling in FA-exacerbated allergic asthma was confirmed by bioinformatic analysis. HIF-1 alpha and its downstream proteins, which are known as mediators of glycolysis, were found to be upregulated by 50 mu M FA, and the FA-enhanced of glycolysis was reversed by inhibition of HIF-1 alpha with PX-478 in vitro and YC-1 in vivo. Furthermore, it was confirmed that inhibition of HIF-1 alpha signaling could restrain the macrophagic inflammatory responses and asthma exacerbation induced by FA. Collectively, these results revealed that FA could exacerbate asthma through the potentiation of HIF-1 alpha-mediated inflammatory responses in macrophages, which also indicated the universal roles of FA-triggered macrophage metabolic and functional alterations in inflammatory or allergic diseases.