Figure 2. Requirement for oxidative metabolism in maturation of anti-inflammatory alternatively activated macrophages .
A) Inhibition or uncoupling of mitochondrial respiration prevents induction of arginase activity by IL-4.
B) Mitochondrial respiration is required for expression of the alternative phenotype, as quantified by induction of various mRNAs.
C–E) Mitochondrial inhibitors diminish the anti-inflammatory effects of IL-4. Control and treated macrophages were costimulated with IFNγ (1 u/ml) / LPS (2.5 ng/ml) in the presence or absence of IL-4 (5 ng/ml). ELISAs were used to quantify the secreted (C) IL-6, (D) IL-12p40 and (E) TNF-α by macrophages. Eto, etomoxir; Oligo, oligomycin. **p < 0.005.
F) IL-4 signaling is intact in macrophages treated with metabolic inhibitors, as measured by induction of PGC-1β and phosphorylation of STAT6.