IL-1R1/MyD88 signaling and the inflammasome are essential in pulmonary inflammation and fibrosis in mice
J. Clin. Invest. Pamela Gasse, et al. 117:3786 doi:10.1172/JCI32285 [Go to this article.]

Figure 4
BLM-induced lung tissue remodeling is IL-1R1 and MyD88 dependent. pro-MMP-9 (99 kDa) and MMP-2 (71 kDa) activities in BALF were analyzed by zymography 1 and 11 days after administration of BLM (15 mg/kg i.n.). Pro-MMP-9 was upregulated in the BALF of WT mice 24 hours after BLM administration and returned to normal levels at day 11, whereas MMP-2 was upregulated only at day 11 after BLM administration (data not shown). (A) Pro-MMP-9 activity was not upregulated in the BALF of MyD88^–/– mice and only partially in IL-1R1^–/– mice 24 hours after BLM administration. (B) MMP-2 was upregulated by BLM in the BALF of WT mice, but less so in MyD88^–/– and IL-1R1^–/– mice on day 11. (C) TIMP-1 as an indicator of a fibrotic process was upregulated in the lungs of WT but not MyD88^–/– or IL-1R1^–/– mice at 24 hours after BLM administration (15 mg/kg). (D) TIMP-1 concentrations were also increased in TLR2 and TLR4 double-deficient mice. TIMP-1 levels were assessed by ELISA, and data represent mean values ± SD from 2 independent experiments (n = 4 mice per group; *P < 0.05; **P < 0.01).