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Pulmonary Emphysema Cross-Linking with Pulmonary Fibrosis and Vice Versa: a Non-usual Experimental Intervention with Elastase and Bleomycin

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Abstract

Elastase (PPE) is usually used for emphysema models, whereas bleomycin (BLM) is used for fibrosis models. The aim of this study was to investigate the effect of BLM in PPE-induced emphysema, as well as the effect of PPE in BLM-induced fibrosis. C57BL/6 mice were divided into five groups: control, PPE, BLM, PPE + BLM, and BLM + PPE. Mice received saline, PPE (3 U/mouse), or BLM (20 U/kg) by intranasal instillation. Mice from the BLM and BLM + PPE groups received BLM on day 0 and saline or PPE on day 21, respectively. Those in the PPE and PPE + BLM groups received PPE on day 0 and saline or BLM on day 21, respectively. Mice were euthanized on day 42. We performed histology, morphometry in lung sections and ELISA, zymography and western blotting in BAL samples or lung homogenates. In the lungs of PPE + BLM and BLM + PPE groups, we observed inflammation, oxidative stress and expression of MMP-2 and MMP-9. The alveolar enlargement was reduced in the PPE + BLM group, suggesting that the BLM could participate in the alveolar remodeling process. The significance of this result supports future therapeutic approaches targeting extracellular-matrix deposition in patients with emphysema as a way to repair the enlargement of alveoli and airspaces.

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Acknowledgments

Isabella Cattani-Cavalieri received a fellowship grant for undergraduate students from CNPq (472417/2012-6). Adriane Graça Reis received a fellowship grant for undergraduate students from FAPERJ (E-26/103.081/2012). Vanessa Pinho Ribeiro received a post-doctoral fellowship grant from CNPq (502917/2012-1). This work was supported by a research grant from FAPERJ E-26/102.254/2013 and from CNPq 400096/2014-5 and 472417/2012-6.

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Authors and Affiliations

  1. Laboratório de Biologia Redox, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Bloco J1-sala 25. Ilha do Fundão, Rio de Janeiro, RJ, CEP 21.941-902, Brazil

    Isabella Cattani-Cavalieri, Adriane Graça Reis, Emanuel Kennedy-Feitosa, Vanessa Pinho-Ribeiro, Manuella Lanzetti, Lycia Brito Gitirana & Samuel Santos Valença

  2. Programa de Pós-graduação em Biologia Humana e Experimental, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

    Bruna Romana-Souza & Luis Cristóvão Porto

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  1. Isabella Cattani-Cavalieri
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Correspondence to Samuel Santos Valença.

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Cattani-Cavalieri, I., Reis, A.G., Kennedy-Feitosa, E. et al. Pulmonary Emphysema Cross-Linking with Pulmonary Fibrosis and Vice Versa: a Non-usual Experimental Intervention with Elastase and Bleomycin. Inflammation 40, 1487–1496 (2017). https://doi.org/10.1007/s10753-017-0590-9

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