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Doxycycline aggravates granulomatous inflammation and lung microstructural remodeling induced by Schistosoma mansoni infection.
Santos, Margarida P; Gonçalves-Santos, Elda; Gonçalves, Reggiani V; Santos, Eliziária C; Campos, Camila C; Bastos, Daniel S S; Marques, Marcos J; Souza, Raquel L M; Novaes, Rômulo D.
Afiliação
  • Santos MP; Institute of Biomedical Sciences, Department of Structural Biology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
  • Gonçalves-Santos E; Institute of Biomedical Sciences, Department of Structural Biology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
  • Gonçalves RV; Department of Animal Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
  • Santos EC; School of Medicine, Federal University of Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil.
  • Campos CC; Institute of Biomedical Sciences, Department of Structural Biology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
  • Bastos DSS; Department of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
  • Marques MJ; Institute of Biomedical Sciences, Department of Pathology and Parasitology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
  • Souza RLM; Institute of Biomedical Sciences, Department of Pathology and Parasitology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
  • Novaes RD; Institute of Biomedical Sciences, Department of Structural Biology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil. Electronic address: romulo.novaes@unifal-mg.edu.br.
Int Immunopharmacol ; 94: 107462, 2021 May.
Article em En | MEDLINE | ID: mdl-33611055
Although doxycycline exhibits immunomodulatory properties, its effects on pulmonary infection by Schistosoma mansoni remain overlooked. Thus, we investigated the impact of this drug on lung granulomatous inflammation and microstructural remodeling in a murine model of schistosomiasis. Swiss mice were randomized in four groups: (i) uninfected, (ii) infected with S. mansoni and untreated, (iii) infected treated with praziquantel (Pzq; 200 mg/kg), and (iv) infected treated with Dox (50 mg/kg). Pz was administered in a single dose, and Dox for 60 days. S. mansoni induced marked granulomatous lung inflammation, which was associated to cytokines upregulation (IL-2, IL-4, IL-10, IFN-γ, TNF-α, and TGF-ß), neutrophils and macrophages recruitment, alveolar collapse, lung fibrosis, and extensive depletion of elastic fibers. These parameters were attenuated by Pzq and aggravated by Dox. Exudative/productive granulomas were predominant in untreated and Dox-treated animals, while fibrotic granulomas were more frequent in Pzq-treated mice. The number and size of granulomas in Dox-treated animals was higher than untreated and Pzq-treated mice. Dox treatment inhibited the increase in MMP-1 and MMP-2 activity but upregulated myeloperoxidase and N-acetylglucosaminidase activity compared to untreated and Pzq-treated animals. Dox and Pzq exerted no effect on elastin depletion and upregulation of elastase activity. Together, our findings indicated that Dox aggravated granulomatous inflammation, accelerating lung microstructural remodeling by downregulating MMP-1 and MMP-2 activity without impair neutrophils and macrophages recruitment or elastase activity. Thus, Dox potentiates inflammatory damage associated with lung fibrosis, elastin depletion and massive alveolar collapse, profoundly subverting lung structure in S. mansoni-infected mice.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esquistossomose mansoni / Doxiciclina / Remodelação das Vias Aéreas / Fatores Imunológicos / Pulmão Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Int Immunopharmacol Assunto da revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esquistossomose mansoni / Doxiciclina / Remodelação das Vias Aéreas / Fatores Imunológicos / Pulmão Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Int Immunopharmacol Assunto da revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda