Figure 5: DCA suppresses macrophage migration in vivo.
From: HIF-1α-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity
(a) (i) LL2 cells (1 × 106) were subctaneously injected in wild-type mice. (ii) Representative immunohistochemical staining of F4/80 (brown) in the isolated tumor from mice with or without DCA treatment (1.5 g l−1 in drinking water for 8 days). (iii) The y axis of the graph represents the number of F4/80-positive stained macrophages per field (10 random fields per tumor). n=7 animals per group. (b) (i) Matrigel (500 μl) containing the supernatant of necrotic cell debris with or without DCA (10 mM) was subctaneously injected in wild-type and LysM HIF-1α KO mice. (ii) Representative immunohistochemical staining of F4/80 (brown) in the isolated matrigel in the presence or absence of DCA. (iii) The y axis represents the number of F4/80-positive macrophages per field (10 random fields per matrigel) in wild-type and LysM HIF-1α KO mice. n=5 animals per group. (c) Mice were pre-treated with DCA (100 mg kg−1 body weight) or PBS for 6 h (n=50 versus 50). Subsequently, endotoxin shock was induced by the intraperitoneal injection of lipopolysaccharide (LPS; Sigma; 40 mg kg−1 body weight). (d) (i) The schema of glucose metabolism. (ii) The schematic representation of classical and active glycolysis in hypoxia. All graphs indicate average with s.d. Student’s t-test was performed to calculate P value. *P<0.05; NS, not significant; wild-type, LysM-Cre−/− HIF-1αflox/flox mice; LysM HIF-1α KO, LysM-Cre+/− HIF-1αflox/flox mice; NEC, the supernatant of necrotic cell debris; Scale bar, 100 μm.
