Skip to main content
. 2010 Mar 1;24(5):491–501. doi: 10.1101/gad.1881410

Figure 3.

Figure 3.

Computational simulation of HIF-1α and HIF-2α expression demonstrated that HIF-α protein abundances are influenced by changes in their mRNA levels. (A) Network diagram of HIF-1α and HIF-2α regulation by LPS, IFNγ, or IL-4, used to construct a mathematical model. (B) Computational simulation of Th1 or Th2 cytokine acting inversely on HIF-1α and HIF-2α mRNA levels, which are unaffected by hypoxia. Transcription rates were altered to the degree measured experimentally in response to Th1 and Th2 cytokines, and the resulting mRNA and protein levels were calculated. Simulations reveal that HIF-1α and HIF-2α protein levels are regulated by the cytokine-mediated control of mRNA synthesis and stability, even in normoxic conditions; this regulatory effect is enhanced in hypoxic conditions. (C) TEPM from VHLflox/flox/LysMcre+/− mice expressed HIF-1α and HIF-2α protein in normoxia. LPS and IFNγ increased HIF-1α, but decreased HIF-2α protein. IL-4 increased HIF-2α protein in VHL-deficient macrophages.