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Acute lung injury is reduced by the α7nAChR agonist PNU-282987 through changes in the macrophage profile.
FASEB J. 2017 01; 31(1):320-332.FJ

Abstract

Nicotinic α-7 acetylcholine receptor (nAChRα7) is a critical regulator of cholinergic anti-inflammatory actions in several diseases, including acute respiratory distress syndrome (ARDS). Given the potential importance of α7nAChR as a therapeutic target, we evaluated whether PNU-282987, an α7nAChR agonist, is effective in protecting the lung against inflammation. We performed intratracheal instillation of LPS to generate acute lung injury (ALI) in C57BL/6 mice. PNU-282987 treatment, either before or after ALI induction, reduced neutrophil recruitment and IL-1β, TNF-α, IL-6, keratinocyte chemoattractant (KC), and IL-10 cytokine levels in the bronchoalveolar lavage fluid (P < 0.05). In addition, lung NF-κB phosphorylation decreased, along with collagen fiber deposition and the number of matrix metalloproteinase-9+ and -2+ cells, whereas the number of tissue inhibitor of metalloproteinase-1+ cells increased (P < 0.05). PNU-282987 treatment also reduced lung mRNA levels and the frequency of M1 macrophages, whereas cells expressing the M2-related markers CD206 and IL-10 increased, suggesting changes in the macrophage profile. Finally, PNU-282987 improved lung function in LPS-treated animals. The collective results suggest that PNU-282987, an agonist of α7nAChR, reduces LPS-induced experimental ALI, thus supporting the notion that drugs that act on α7nAChRs should be explored for ARDS treatment in humans.-Pinheiro, N. M., Santana, F. P. R., Almeida, R. R., Guerreiro, M., Martins, M. A., Caperuto, L. C., Câmara, N. O. S., Wensing, L. A., Prado, V. F., Tibério, I. F. L. C., Prado, M. A. M., Prado, C. M. Acute lung injury is reduced by the α7nAChR agonist PNU-282987 through changes in the macrophage profile.

Authors+Show Affiliations

Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, Brazil.Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, Brazil. Department of Biological Science, Universidade Federal de São Paulo, Diadema, Brazil.Department of Immunology, Universidade de São Paulo, São Paulo, Brazil.Department of Biological Science, Universidade Federal de São Paulo, Diadema, Brazil.Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, Brazil.Department of Biological Science, Universidade Federal de São Paulo, Diadema, Brazil.Department of Immunology, Universidade de São Paulo, São Paulo, Brazil.Department of Immunology, Universidade de São Paulo, São Paulo, Brazil.Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada. Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada; and.Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, Brazil.Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada. Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada; and.Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, Brazil; carla.prado@unifesp.br. Department of Bioscience, Federal University of São Paulo, Campus Baixada Santista, Santos, Brazil.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27729414

Citation

Pinheiro, Nathalia M., et al. "Acute Lung Injury Is Reduced By the α7nAChR Agonist PNU-282987 Through Changes in the Macrophage Profile." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 31, no. 1, 2017, pp. 320-332.
Pinheiro NM, Santana FP, Almeida RR, et al. Acute lung injury is reduced by the α7nAChR agonist PNU-282987 through changes in the macrophage profile. FASEB J. 2017;31(1):320-332.
Pinheiro, N. M., Santana, F. P., Almeida, R. R., Guerreiro, M., Martins, M. A., Caperuto, L. C., Câmara, N. O., Wensing, L. A., Prado, V. F., Tibério, I. F., Prado, M. A., & Prado, C. M. (2017). Acute lung injury is reduced by the α7nAChR agonist PNU-282987 through changes in the macrophage profile. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 31(1), 320-332. https://doi.org/10.1096/fj.201600431R
Pinheiro NM, et al. Acute Lung Injury Is Reduced By the α7nAChR Agonist PNU-282987 Through Changes in the Macrophage Profile. FASEB J. 2017;31(1):320-332. PubMed PMID: 27729414.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acute lung injury is reduced by the α7nAChR agonist PNU-282987 through changes in the macrophage profile. AU - Pinheiro,Nathalia M, AU - Santana,Fernanda P R, AU - Almeida,Rafael Ribeiro, AU - Guerreiro,Marina, AU - Martins,Milton A, AU - Caperuto,Luciana C, AU - Câmara,Niels O S, AU - Wensing,Lislaine A, AU - Prado,Vânia F, AU - Tibério,Iolanda F L C, AU - Prado,Marco Antônio M, AU - Prado,Carla M, Y1 - 2016/10/11/ PY - 2016/04/18/received PY - 2016/09/28/accepted PY - 2016/10/13/pubmed PY - 2017/8/30/medline PY - 2016/10/13/entrez KW - ARDS KW - acetylcholine experimental model KW - lung inflammation KW - nicotine receptor KW - nicotinic agonist SP - 320 EP - 332 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. VL - 31 IS - 1 N2 - Nicotinic α-7 acetylcholine receptor (nAChRα7) is a critical regulator of cholinergic anti-inflammatory actions in several diseases, including acute respiratory distress syndrome (ARDS). Given the potential importance of α7nAChR as a therapeutic target, we evaluated whether PNU-282987, an α7nAChR agonist, is effective in protecting the lung against inflammation. We performed intratracheal instillation of LPS to generate acute lung injury (ALI) in C57BL/6 mice. PNU-282987 treatment, either before or after ALI induction, reduced neutrophil recruitment and IL-1β, TNF-α, IL-6, keratinocyte chemoattractant (KC), and IL-10 cytokine levels in the bronchoalveolar lavage fluid (P < 0.05). In addition, lung NF-κB phosphorylation decreased, along with collagen fiber deposition and the number of matrix metalloproteinase-9+ and -2+ cells, whereas the number of tissue inhibitor of metalloproteinase-1+ cells increased (P < 0.05). PNU-282987 treatment also reduced lung mRNA levels and the frequency of M1 macrophages, whereas cells expressing the M2-related markers CD206 and IL-10 increased, suggesting changes in the macrophage profile. Finally, PNU-282987 improved lung function in LPS-treated animals. The collective results suggest that PNU-282987, an agonist of α7nAChR, reduces LPS-induced experimental ALI, thus supporting the notion that drugs that act on α7nAChRs should be explored for ARDS treatment in humans.-Pinheiro, N. M., Santana, F. P. R., Almeida, R. R., Guerreiro, M., Martins, M. A., Caperuto, L. C., Câmara, N. O. S., Wensing, L. A., Prado, V. F., Tibério, I. F. L. C., Prado, M. A. M., Prado, C. M. Acute lung injury is reduced by the α7nAChR agonist PNU-282987 through changes in the macrophage profile. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/27729414/Acute_lung_injury_is_reduced_by_the_α7nAChR_agonist_PNU_282987_through_changes_in_the_macrophage_profile_ L2 - http://www.fasebj.org/doi/full/10.1096/fj.201600431R?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -