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Doxycycline impairs neutrophil migration to the airspaces of the lung in mice exposed to intratracheal lipopolysaccharide

Andres Moon1, Sucheol Gil1, Sean E Gill2, Peter Chen1 and Gustavo Matute-Bello1*

Author Affiliations

1 The Center for Lung Biology, Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Washington School of Medicine, 850 Republican Street, Box 358052, Seattle, 98109-4714, , WA, USA

2 The Centre for Critical Illness Research, Lawson Health Research Institute, Department of Medicine, Western University, London, ON, Canada

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Journal of Inflammation 2012, 9:31  doi:10.1186/1476-9255-9-31

Published: 3 September 2012

Abstract

Background

Tetracyclines are broad-spectrum antibiotics that are also used to induce gene expression using the reverse tetracycline transactivator / tetracycline operator system (rtTA/tetO system). The system assumes that tetracyclines have no effects on mammals. However, a number of studies suggest that tetracyclines may have powerful anti-inflammatory effects. We report that the tetracycline, doxycycline, inhibits neutrophil (PMN) influx into the lungs of mice treated with bacterial endotoxin (LPS).

Methods

Mice were challenged with intratracheal LPS in the presence or absence of doxycyline. bronchoalveolar lavage cell counts and differential, total bronchoalveolar lavage protein, lung homogenate caspase-3 and tissue imaging were used to assess lung injury. In addition, PMN chemotaxis was measured in vitro and syndecan-1 was measured in bronchoalveolar lavage fluid.

Results

The administration of doxycycline resulted in a significant decrease in the number of bronchoalveolar lavage PMNs in LPS-treated mice. Doxycycline had no effect on other markers of lung injury such as total bronchoalveolar lavage protein and whole lung caspase-3 activity. However, doxycycline resulted in a decrease in shed syndecan-1 in bronchoalveolar lavage fluid.

Conclusion

We conclude that doxycycline has an important anti-inflammatory effect that can potentially confound the experiments in which the rtTA/tetO system is being used to study the immune response.

Keywords:
Doxycycline neutrophils lipopolysaccharide inflammation