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. 2016 May 31;71(12):1145–1153. doi: 10.1136/thoraxjnl-2015-207402

Figure 3.

Figure 3

Hypoxia increases Mycobacterium tuberculosis (M.tb)-driven matrix metalloproteinase-1 (MMP-1) expression and secretion by human monocyte-derived macrophages (MDMs). (A) Hypoxia (1% pO2) increases MMP-1 gene expression in primary human MDMs infected with M.tb at 24 h. (B) Hypoxia increases intracellular MMP-1 accumulation on confocal microscopy at 72 h in MDMs infected with M.tb (MOI=1) compared with normoxia or control uninfected cells. (C) Mtb infection increases MMP-1 secretion by infected MDMs greater than LPS (100 ng/mL) in both normoxia and hypoxia analysed 72 h after infection. (D) MMP-1 activity is increased in M.tb-infected but not control human macrophages analysed by casein zymography, and hypoxia further increases caseinolytic activity. (E) Stabilisation of hypoxia-inducible factor (HIF)-1α by dimethyloxalyl glycine (DMOG) (range 0.05–0.5 mM) significantly increases MMP-1 secretion analysed by ELISA and proteolytic activity measured by zymography in a dose-dependent manner. N=21% O2; 5% CO2, H=1% O2; 5% CO2. ****p<0.0001, ***p<0.001, **p<0.01, *p<0.05. LPS, lipopolysaccharide.