The online version of this article (doi:10.1186/1476-9255-9-31) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
AM performed the animal experiments and participated in the drafting of the manuscript. SG performed immunoassays and flow cytometry and participated in the drafting of the manuscript. SEG performed the chemotaxis assays and participated in editing the manuscript. PC performed syndecan-1 dot blot assays and participated in the drafting of the manuscript. GMB conceived the study, participated in its design and coordination and drafted the manuscript. All the authors approved the final version of the manuscript.
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).
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.
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.
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.
Authors’ original file for figure 112950_2011_242_MOESM1_ESM.jpeg
Authors’ original file for figure 212950_2011_242_MOESM2_ESM.jpeg
Authors’ original file for figure 312950_2011_242_MOESM3_ESM.jpeg
Authors’ original file for figure 412950_2011_242_MOESM4_ESM.jpeg
Authors’ original file for figure 512950_2011_242_MOESM5_ESM.jpeg
Authors’ original file for figure 612950_2011_242_MOESM6_ESM.jpeg
Tanino Y, Coombe DR, Gill SE, Kett WC, Kajikawa O, Proudfoot AE, Wells TN, Parks WC, Wight TN, Martin TR, Frevert CW: Kinetics of chemokine-glycosaminoglycan interactions control neutrophil migration into the airspaces of the lungs. J Immunol. 2010, 184: 2677-2685. 10.4049/jimmunol.0903274. PubMedCentralCrossRefPubMed
Golub LM, Ramamurthy NS, McNamara TF, Greenwald RA, Rifkin BR: Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs. Crit Rev Oral Biol Med. 1991, 2: 297-321. PubMed
Gueders MM, Bertholet P, Perin F, Rocks N, Maree R, Botta V, Louis R, Foidart JM, Noel A, Evrard B, Cataldo DD: A novel formulation of inhaled doxycycline reduces allergen-induced inflammation, hyperresponsiveness and remodeling by matrix metalloproteinases and cytokines modulation in a mouse model of asthma. Biochem Pharmacol. 2008, 75: 514-526. 10.1016/j.bcp.2007.09.012. CrossRefPubMed
Nuesch E, Rutjes AW, Trelle S, Reichenbach S, Juni P: Doxycycline for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2009, CD007323-
- Doxycycline impairs neutrophil migration to the airspaces of the lung in mice exposed to intratracheal lipopolysaccharide
Sean E Gill
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II