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MHTP, 2-Methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl) phenol, a Synthetic Alkaloid, Induces IFN-γ Production in Murine Model of Ovalbumin-Induced Pulmonary Allergic Inflammation

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Abstract

MHTP [2-methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl) phenol], a synthetic isoquinolinic alkaloid, presented anti-inflammatory activity in several experimental models of acute inflammation as lipopolysaccharide (LPS)-induced acute lung injury and phlogistic agent-induced edema and presented low preclinical toxicity. The aim of this study was to determine the MHTP effect on ovalbumin (OVA)-induced pulmonary allergic inflammation. In other to realize this study, female BALFB/c mice were sensitized and challenged with OVA (OVA group) and treated with MHTP (MHTP group) by nasal instillation. Inflammatory, allergic, and immunomodulatory parameters such as migration of inflammatory cells to the lung tissue, pulmonary histological analysis, serum level of IgE-allergen specific, cytokine secretion, and lung T cell population characterization were analyzed and the data were considered statistically significant with p < 0.05. OVA-sensitized and OVA-challenged and MHTP (5.0 mg/kg)-treated mice presented reduction on total leukocyte migration into the bronchoalveolar lavage (BALF) dependent of lymphocyte and eosinophil migration (p < 0.001 and p < 0.01) as compared with the OVA group. Flow cytometric analysis showed that MHTP treatment decreased the percentage of granulocytes (p < 0.001) into the BALF and lung tissue histological analyzes demonstrated that the MHTP treatment decreased leukocyte migration and mucus production. In addition, treatment with MHTP decreased the number of CD3+CD4+ T cells independently of CD8+ T cell reduction into the BALF. The treatment also reduced significantly (p < 0.05) the serum level of IgE-OVA specific followed by reduction of IL-4, IL-13, and IL-17 production. Surprisingly, the MHTP treatment increased significantly (p < 0.05) the IFN-γ production in the BALF of these animals. Therefore, the results presented here showed that MHTP treatment, by nasal instillation, in a mouse model of OVA-induced pulmonary allergy has anti-allergic and immunomodulatory effects dependent on a Th1-skewed cytokine production that ameliorate the pulmonary allergic inflammation.

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Acknowledgments

The Brazilian government sponsored this study by CNPq and CAPES organization.

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Authors and Affiliations

  1. Department of Physiology and Pathology, Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa, PB, Brazil

    Laércia K. D. Paiva Ferreira, Larissa A. M. Paiva Ferreira, Adriano Francisco Alves & Marcia Regina Piuvezam

  2. São Francisco da Paraíba College, Cajazeiras, PB, Brazil

    Fagner Carvalho Leite

  3. Postgraduate Program in Development and Technological Innovation in Medicines, Federal University of Paraíba, João Pessoa, PB, Brazil

    Luiz A. de Araújo Silva & Luís Cezar Rodrigues

  4. Department of Morphology, Health Sciences Center, Federal University of Paraíba, João Pessoa, PB, Brazil

    Giciane Carvalho Vieira

  5. Universidade Federal da Paraíba, Campus I, PO 5009, João Pessoa, PB, 58–051–970, Brazil

    Marcia Regina Piuvezam

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  1. Laércia K. D. Paiva Ferreira
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Correspondence to Marcia Regina Piuvezam.

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The manipulation of the animals was performed according to animal care guide. The Committee on Ethics in Animal Use (CEUA/UFPB) approved the experimental procedures under certificate no. 3105/14.

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Paiva Ferreira, L.K.D., Paiva Ferreira, L.A.M., Alves, A.F. et al. MHTP, 2-Methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl) phenol, a Synthetic Alkaloid, Induces IFN-γ Production in Murine Model of Ovalbumin-Induced Pulmonary Allergic Inflammation. Inflammation 41, 2116–2128 (2018). https://doi.org/10.1007/s10753-018-0855-y

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