Formaldehyde reinforces pro-inflammatory responses of macrophages through induction of glycolysis.

Abstract Formaldehyde (FA) is widely used in chemical industry, which is also known as a common indoor air pollutant. Exposure of FA has been associated with multiple detrimental health effects. Our previous study showed that FA could inhibit the development of T lymphocytes in mice, leading to impaired immune functions. Macrophages are important innate immune cells which trigger inflammatory responses in tissues. In the present study, FA exposure at 2.0 mg/m3 was found to enhance the pro-inflammatory responses of macrophages in male BALB/c mice, which was confirmed by elevated pro-inflammatory cytokine release and NO secretion in macrophages isolated from the FA-exposed mice and in vitro macrophage models upon lipopolysaccharide stimulation. Glycolysis is the key metabolic process for the classical activation of macrophages, which was found to be elevated in the in vitro macrophage models treated with FA at 50 and 100 μM concentrations for 18 h. HIF-1α and the associated proteins in its signaling cascade, which are known to mediate glycolytic metabolism and inflammatory responses, were found to be upregulated by 50 and 100 μM FA in THP-1 derived and RAW264.7 macrophage models, and the enhanced pro-inflammatory responses induced by 100 μM FA were reversed by inhibitory compounds interfering with glucose metabolism or suppressing HIF-1α activity. Collectively, the results in this study revealed that FA could enhance the pro-inflammatory responses of macrophages through the induction of glycolysis, which outlined the FA-triggered metabolic and functional alterations in immune cells.