[Inhibition of pulmonary fibrosis by doxycycline: an experiment with mice].
OBJECTIVE
To investigate the effect of doxycycline, an antimicrobial antibiotic inhibiting type IV collagenase, on the development of pulmonary fibrosis induced by bleomycin (BLM) in mice.


METHODS
Gelatin zymography assay was used to detect the secretion of 72,000 and 92,000 type IV collagenase in HT-1080 cells and the activity of these enzymes in vitro. Experimental pulmonary fibrosis was induced by intra-tracheal administration of BLM in anesthetized mice. Total lung collagen content was determined by hydroxyproline assay. The histopathological changes of pulmonary fibrosis were evaluated by image analysis.


RESULTS
The secretion of 72,000 and 92,000 type IV collagenase in HT-1080 cell was markedly inhibited by doxycycline at concentrations of 0.1 mg/ml and 0.05 mg/ml. The activity of type IV collagenase in vitro was also suppressed by doxycycline. The hydroxyproline level in the lung was decreased in mice treated with doxycycline at the dose of 100 mg/kg, down to 34.7% of that of the BLM model group. As shown by image analysis, the extensiveness of fibrotic lesions, the thickness of interalveolar septa, and the accumulation of nucleated cells were decreased in doxycycline treated group in comparison with BLM model group.


CONCLUSIONS
This study provides evidence that doxycycline shows inhibitory effect on BLM induced pulmonary fibrosis.
Huang
Yun-hong
YH
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Li
Yi
Y
Shang
Yue
Y
Ouyang
Zhi-gang
ZG
Zhen
Yong-su
YS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001761:Bleomycin / Q000633:toxicity; D045744:Cell Line, Tumor; D017364:Collagenases / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008813:Mice, Inbred ICR; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D061965:Matrix Metalloproteinase Inhibitors; D001761:Bleomycin; D017364:Collagenases; D004318:Doxycycline; D006909:Hydroxyproline