Hypoxic up-regulation of IL-1β by human MDMs in vitro and by TAMs in hypoxic areas of murine mammary tumors: role of HIF-1 and -2. (A) IL-1β mRNA levels and protein release by human MDMs after their exposure to normoxia (20.9% O2; N) or hypoxia (0.1% O2; H) for 18 hours, or hypoxia for 18 hours after exposure to siRNA for HIF-1 α (1 α), HIF-2α (2 α), both HIFs-1α and -2α together (1α + 2α), or a scrambled control (Scr). (B) Hypoxic induction of IL-1β mRNA by BMDMs from wild-type mice and mice bearing a myeloid cell-specific knockout of the HIF-1 α gene. (C) Up-regulated expression of IL-1β by F4/80+ macrophages in pimonodazole-stained (ie, hypoxic; H) compared with pimonodazole-unstained (ie, normoxic; N) areas of murine mammary (4T1) tumors (yellow arrows on the merged H image). Pooled data from 3 replicate experiments are shown. *P < .05 compared with corresponding normoxic group. ∧P < .05 compared with the Scr siRNA/hypoxia group. +P < .05 compared with macrophages from wild-type mice exposed to hypoxia.
