Abstract
Hypoxia is associated with inflammation and various chronic diseases. Folic acid is known to ameliorate inflammatory reactions, but the metabolism of folic acid protecting against hypoxia-induced injury is still unclear. In our study, we examined the inflammatory signal transduction pathway in human promyelomonocytic cells (THP-1 cells) with or without treatment with folic acid under hypoxic culture conditions. Our results indicated that supplementation with folic acid significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in hypoxic conditions. Treating THP-1 cells with folic acid suppressed oxidative stress and hypoxia-inducible factor-1α in a dose-dependent manner. Folic acid targeted the activation of Janus kinase 2, downregulated the phosphorylation of signal transducer and activator of transcription 3, and decreased the expression of nuclear factor-κB p65 protein in cells. However, the absence of folic acid did not make cells more vulnerable under hypoxic conditions. In conclusion, folic acid efficiently inhibited the inflammatory response of THP-1 cells under hypoxic conditions by inhibiting reactive oxygen species production and the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. Our study supports a basis for treatment with folic acid for chronic inflammation, which correlated with hypoxia.
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