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

by Selleckchem | Jul 08 2023

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/m3 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-1β, TNF-α, IL-6 and IL-8, were increased in lung and serum of FA-exposed asthmatic mice. The contribution of HIF-1α signaling in FA-exacerbated allergic asthma was confirmed by bioinformatic analysis. HIF-1α and its downstream proteins, which are known as mediators of glycolysis, were found to be upregulated by 50 μM FA, and the FA-enhanced of glycolysis was reversed by inhibition of HIF-1α with PX-478 in vitro and YC-1 in vivo. Furthermore, it was confirmed that inhibition of HIF-1α 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-1α-mediated inflammatory responses in macrophages, which also indicated the universal roles of FA-triggered macrophage metabolic and functional alterations in inflammatory or allergic diseases.

Comments:

The passage you provided describes a study that investigated the molecular basis of the correlation between formaldehyde (FA) exposure and allergic asthma. The study used a murine (mouse) model of asthma induced by ovalbumin (OVA) and found that inhaling 2.0 mg/m3 of FA for 2 weeks exacerbated pulmonary inflammation and mucus over-accumulation in the asthmatic mice.

The researchers also observed an increase in pro-inflammatory cytokines, specifically IL-1β, TNF-α, IL-6, and IL-8, in the lungs and serum of the FA-exposed asthmatic mice. Through bioinformatic analysis, the study confirmed the involvement of HIF-1α signaling in the exacerbation of allergic asthma by FA.

HIF-1α is a protein involved in various cellular processes, including glycolysis (the breakdown of glucose). The study found that exposure to 50 μM of FA upregulated HIF-1α and its downstream proteins, which are known to be involved in glycolysis. Inhibition of HIF-1α using PX-478 in vitro and YC-1 in vivo reversed the FA-enhanced glycolysis.

Furthermore, the study demonstrated that inhibiting HIF-1α signaling could restrain macrophagic inflammatory responses and asthma exacerbation induced by FA. This suggests that FA exacerbates asthma through the potentiation of HIF-1α-mediated inflammatory responses in macrophages.

Overall, these findings shed light on the molecular mechanisms underlying the correlation between FA exposure and allergic asthma. They suggest that FA-triggered alterations in macrophage metabolism and function play a role in inflammatory and allergic diseases.