| First Author | Riffo-Vasquez Y | Year | 2012 |
| Journal | Am J Respir Cell Mol Biol | Volume | 47 |
| Issue | 2 | Pages | 245-52 |
| PubMed ID | 22447969 | Mgi Jnum | J:199771 |
| Mgi Id | MGI:5504594 | Doi | 10.1165/rcmb.2011-0412OC |
| Citation | Riffo-Vasquez Y, et al. (2012) Mycobacterium tuberculosis chaperonin 60.1 inhibits leukocyte diapedesis in a murine model of allergic lung inflammation. Am J Respir Cell Mol Biol 47(2):245-52 |
| abstractText | Chaperonin 60.1 from Mycobacterium tuberculosis suppressed allergic lung inflammation and bronchial hyperresponsiveness in mice by a mechanism that is yet to be clarified. To investigate the possible antiinflammatory mechanism(s) of action of Cpn60.1 in a model of allergic lung inflammation, ovalbumin (OVA)-allergic mice were pretreated with Cpn60.1 intranasally 20 minutes before each OVA aerosol challenge in a total of three treatments. Readouts were performed 24 hours after last challenge. Pretreatment with Cpn60.1 (1.0-0.001 mug) significantly inhibited the number of eosinophils in bronchoalveolar lavage fluid (OVA, 49.2 +/- 12.3 versus Cpn60.1 [1 mug dose], 90.4 +/- 2.3 x 10(4) cells/ml) and IL-5 release (OVA, 43 +/- 8.5 versus Cpn60.1 [1 mug dose], 3 +/- 11 pg/ml) but increased IL-12 levels (OVA, 50 +/- 24 versus Cpn60.1 [1 mug dose], 103 +/- 13 pg/ml). The effect of Cpn60.1 on cell recruitment and IL-5, but not IL-12, release was abolished in TLR-4 knockout mice. Intravital microscopy demonstrated that Cpn60.1 reduced chemokine-mediated leukocyte rolling and transmigration across the vessel wall (rolling cells: eotaxin, 11.7 +/- 1.1 versus Cpn60.1 [1 mug dose], 2.8 +/- 1 cells in 30 s). Similarly, Cpn60.1 reduced eotaxin-induced leukocyte migration in vitro (eotaxin, 17.3 +/- 3.3 versus Cpn60.1 [0.1 mug dose], 3.3 +/- 0.4 cells x 10(4)/ml). Immunostaining demonstrated that Cpn60.1 inhibits VCAM-1 and increases vascular endothelial-cadherin expression in lung vascular tissue, suggesting that the antiinflammatory effect of Cpn60.1 is partly mediated by altering the expression of adhesion molecules. This study shows that Cpn60.1 inhibits leukocyte diapedesis by a TLR-4 and an adhesion molecule-dependent mechanism in allergic inflammation in mice. |
