Bleomycin and Paraquat Mediated Pulmonary Fibrosis Is IL-17 Independent
Alexandre T Fabro, Edwin R Parra, Mariestela P Ragel, Walcy R Teodoro, Helmut H Popper, Vera L Capelozzi. Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Medical University Graz, Graz, Austria
Background: Pulmonary fibrosis is a destructive process that in many cases are of unknown cause such as idiopathic pulmonary fibrosis. Better characterization of the immunological mechanisms of pulmonary fibrosis is needed to identify new therapeutic modalities for these diseases. The aim of the current study was to characterize the mechanisms of pulmonary fibrosis in the late phase and to determine whether IL-17A plays an important regulatory role.
Design: The pulmonary fibrosis was induced in distinct animal models, including Bleomycin (B-BLM) and Paraquat (B-PQ) in Balb/c mice. Additionally, IL17-RA Knockout (IL17KO) and wild C57 mice (C-BLM) were included. We used the picrosirius-polarization method and weigert's resorcin-fuchsin stain to morphometric study the peribronchiolar collagen and elastic fibers, respectively. By immunohistochemistry, we evaluate TGF-β, IL-21, IL-6, CD83, IL-17, IL-23, IL-13, STAT3, PDGF, FGF, TNF-α and limphocytic markers expression, using stereology method. The sacrifice of mice was performed 21 day after induction.
Results: We report here that late PQ and BLM-mediated peribronchiolar fibrosis is IL-17 independent, as IL17-RA -/- mice developed similar peribronchiolar fibrosis after induction when compared to B-BLM, B-PQ and C-BLM (Fig left). We found that only B-BLM and B-PQ presented increase of elastic fibers and they show a positive correlation with the deposition of collagen fibers. In IL-17KO group TGF and collagen correlated. The B-BLM showed marked increase in dendritic cells (CD83) and T lymphocytes (CD3), but the IL-17 axis is suppressed by low expression of IL-23, IL-13 and IL-17 (tendency). In contrast, the mice without IL-17A receptor (IL17KO) showed overexpression of IL-17 axis by high expression of IL-17, IL-6, IL-21, STAT3 and CD8+ T cell. The B-PQ group has only increased FGF-β.
Conclusions: Bleomycin and paraquat-mediated peribronchiolar fibrosis is IL-17 independent in the late phase. However, distinct mechanisms of peribronchiolar fibrosis may be involved, such as IL-17 response in C57 mice and presentation and processing of antigens in Balb/c mice. More studies are necessary to validate the regulatory role of IL-17 on pulmonary fibrosis process.
Financial Support: FAPESP, CNPq
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 301, Wednesday Morning