AP-1 Decoy modulating MMP-2/TIMP-1 imbalance induced by bleomycin-A5 in pulmonary fibroblasts / 中华劳动卫生职业病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of AP-1 Decoy on matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-1) imbalance induced by bleomycin-A5 (BLM-A5) in pulmonary fibroblasts.</p><p><b>METHODS</b>Pulmonary fibroblasts were primary cultured, and transferred with AP-1 Decoy before treated with BLM-A5. MMPs activity in medium was determined by gelatin zymography. Protein content of TIMP-1 in medium was detected by ELISA. Expression of MMP-2 mRNA and TIMP-1 mRNA were determined by reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>BLM-A5 induced the increase in activity of MMP-2 at 12 h [A (0.77 +/- 0.08) vs (0.65 +/- 0.07) P < 0.05], but it was suppressed by AP-1 Decoy [A (0.68 +/- 0.05)]. BLM-A5 up-regulated the expression of protein and mRNA of TIMP-1 after 12 h, and 24 h [(39.3 +/- 4.3), (46.3 +/- 4.8) ng/ml vs (28.9 +/- 2.7), (31.6 +/- 2.4) ng/ml] and [Absorbance ratio to beta-actin (0.94 +/- 0.13, 1.08 +/- 0.06) vs (0.76 +/- 0.07, 0.75 +/- 0.08)] (P < 0.05 or P < 0.01) but AP-1 Decoy modulated the up-regulation. All these indexes in AP-1 Decoy group had no significant difference in contrast to the normal group. Mutant AP-1 Decoy had not the same function as AP-1 Decoy on the expression of MMP-2 and TIMP-1 in pulmonary fibroblasts.</p><p><b>CONCLUSION</b>AP-1 Decoy inhibits the increase in MMP-2 activity and the up-regulation of TIMP-1 induced by BLM-A5 in pulmonary fibroblasts.</p>