Figure 5.

Speculative scheme of how the putative HIF-GC crosstalk occurs in inflammation. We speculate that HIF can negatively regulate pomca expression to control not only its own activity but also that of glucocorticoids throughout the inflammatory process. Indeed, if not properly controlled, glucocorticoids could upregulate GILZ, whose overexpression has been demonstrated to suppress NF-κB activation. Since the latter can, in turn, increase the transcription of HIF-1α in response to hypoxic and inflammatory stimuli, its downregulation would hamper HIF activation and avoid essential pro-inflammatory HIF-mediated effects to occur.