Publikationsdatenbank

Teaching Veterinary Pathologie in the 21th century - application of e-learning modules (2005)

Art

Vortrag

Autoren

Pospischil, A.

Suter, M.

Gruber, A.

Biolatti, B.

Kongress

23th meeting of the ESVP

Neapel/Italien, 07. – 10.09.2005

Quelle

Sprache

Englisch

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

To elucidate genes important in development or repair of asbestos induced lung-diseases, gene expression was examined in mice after inhalation of chrysotile asbestos for 3, 9 and 40 days. We identified changes in the expression of genes linked to proliferation (cyclin B2, CDC20 and CDC28 protein kinase regulatory subunit 2), inflammation (CCL9, CCL 6, complement component 1, chitinase3-like 3, TNF superfamily member 10 and IL-1B) and matrix remodeling (MMP12, MMp3, integrin αX, and cathepsins K, Z, B and S). The most highly induced gene at all timepoints was mclca3 (gob5), a putative calcium-activated chloride channel involved in the regulation of mucus production and/or secretion. Using histochemistry, we demonstrated accumulation of mucus and increased mClca3 protein in the bronchiolar epithelium of asbestos-exposed mice at all time points but peaking at 9 days. Cytokine levels (interleukin-1β, interleukin-4, interleukin-6) 9n bronchoalveolar lavage fluid also increased at 9 days, suggesting Th2-mediated immunity may play a role in asbestos induced mucus production. In contrast, levels of cathepsin K, a potent elstase, increased between 3 and 40 days at both the mRNA and protein levels, localizing primarily in CD45-positive leukocytes and interstitial cells, identification of genes involved in lung injury and remodeling after asbestos exposure could aid in defining mechanisms of airborne particulate-induced disease and in developing therapeutic strategies.