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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Acute lung injury is reduced by the alpha 7nAChR agonist PNU-282987 through changes in the macrophage profile

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Pinheiro, Nathalia M. ; Santana, Fernanda P. R. ; Almeida, Rafael Ribeiro ; Guerreiro, Marina ; Martins, Milton A. ; Caperuto, Luciana C. ; Camara, Niels O. S. ; Wensing, Lislaine A. ; Prado, Vania F. ; Tiberio, Iolanda F. L. C. ; Prado, Marco Antonio M. ; Prado, Carla M.
Total Authors: 12
Document type: Journal article
Source: FASEB JOURNAL; v. 31, n. 1, p. 320-332, JAN 2017.
Web of Science Citations: 0
Abstract

Nicotinic alpha-7 acetylcholine receptor (nAChR alpha 7) is a critical regulator of cholinergic anti-inflammatory actions in several diseases, including acute respiratory distress syndrome (ARDS). Given the potential importance of alpha 7nAChR as a therapeutic target, we evaluated whether PNU-282987, an alpha 7nAChR agonist, is effective in protecting the lung against inflammation. We performed intratracheal instillation of LPS to generate acute lung injury (ALI) in C57BL/6mice. PNU-282987 treatment, either before or after ALI induction, reduced neutrophil recruitment and IL1 beta, TNF-alpha, IL-6, keratinocyte chemoattractant (KC), and IL-10 cytokine levels in the bronchoalveolar lavage fluid (P<0.05). In addition, lung NF-kappa B 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, anagonist of alpha 7nAChR, reduces LPS-induced experimental ALI, thus supporting the notion that drugs that act on alpha 7nAChRs 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., Camara, N. O. S., Wensing, L. A., Prado, V. F., Tiberio, I. F. L. C., Prado, M. A. M., Prado, C. M. Acute lung injury is reduced by the alpha 7nAChR agonist PNU-282987 through changes in the macrophage profile. (AU)

FAPESP's process: 13/02881-4 - Effects of cholinergic function deficiency on pulmonary mechanics and histopathology in an experimental model of acute inflammation induced by LPS instillation in genetically modified mice
Grantee:Nathalia Montouro Pinheiro
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
Grantee:Niels Olsen Saraiva Câmara
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/25689-4 - Effects of cholinergic system in acute and chronic pulmonary inflammation
Grantee:Carla Máximo Prado
Support type: Regular Research Grants