Hypoxia-inducible Factor 1 as one of the “Signaling Drivers” of Toll-like Receptor-Dependent and Allergic Inflammation

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription complex which plays a crucial role in cellular adaptation to low oxygen availability. In the last years there has been increasing evidence about the role of this factor in inflammatory/innate immune reactions. It has also been found to contribute to different types of allergic inflammation. In this review the current knowledge about the accumulation and role of HIF-1 in Toll-like receptor-mediated and allergic inflammation is summarized. Differential biochemical mechanisms employed to stabilize the protein in different cases are discussed.

Placental Regulation of Inflammation and Hypoxia after TNF‐α Infusion in Mice

“…The observed correlation between Hif-1a expression and mFlt-1, sFlt-1, Tlr-3 and Tlr-4 expression supports the growing body of work, showing that there is a link between this key placental transcription factor and molecules involved in angiogenesis 58,68 and inflammation. 40,59,69 These results support a role for maladaptive regulation of TLR and HIF-1a initiated by an imbalance in inflammatory cytokines in the pathogenesis of pre-eclampsia. Alterations in these key molecules that sense and respond to changes in the cellular environment may be implicated in the abnormal development of the placenta that leads to the maternal signs of hypertension and proteinuria and may provide a target for treatment in human disease.…”

“…30 It is also emerging as one of the 'signalling drivers' of TLR dependent inflammation. 59 While oxygen levels regulate HIF-1a activity by affecting either its stability or its transcriptional ability, de novo synthesis of HIF-1a is largely dependent upon non-hypoxic mechanisms such as growth factors and inflammatory stimuli. Hif-1a mRNA has been previously demonstrated to be upregulated by inflammatory stimuli such as TNF-a 37 or TLR-4 activation, 39 whereas expression has been reported to be unchanged 60,61 or only modestly increased 62 following hypoxia.…”

Interleukin-1 beta induces the expression and production of stem cell factor by epithelial cells: crucial involvement of the PI-3K/mTOR pathway and HIF-1 transcription complex

“…This is most likely due to a high dependence of the cells on glycolysis during inflammatory stimulation (with IL-1b in our case). 9 Glycolysis depends on both HIF-1-controlled transcription and mTOR-induced translation processes. Therefore, glycolysis was limited upon Figure 6 mTOR is crucially involved in IL-1b-induced SCF production.…”

“…9 In theory, this mechanism could be responsible for triggering inflammatory activation of SCF production in the target cells.…”

The Therapeutic Effect of Chelidonic Acid on Ulcerative Colitis

“…37) Hypoxia signaling pathways are involved in the inflammatory process, and HIF-1α serves as a marker of inflammatory disease. 38,39) HIF-1α, a hypoxia-mediated gene regulating transcription factor, is accumulated in the case of toll-like receptors (TLR)-mediated inflammatory reactions. 40) It has been reported that HIF-1α is overexpressed in colitis affected human and murine colon tissues.…”