Folic acid supplementation repressed hypoxia-induced inflammatory response via ROS and JAK2/STAT3 pathway in human promyelomonocytic cells

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-1 beta and tumor necrosis factor-a in hypoxic conditions. Treating THP-1 cells with folic acid suppressed oxidative stress and hypoxia-inducible factor-1 alpha 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-kappa B 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. (C) 2018 Elsevier Inc. All rights reserved.