| Full text | |
| Author(s): Show less - |
Pinheiro, Nathalia M.
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Santana, Fernanda P. R.
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Almeida, Rafael Ribeiro
;
Guerreiro, Marina
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Martins, Milton A.
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Caperuto, Luciana C.
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Camara, Niels O. S.
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Wensing, Lislaine A.
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Prado, Vania F.
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Tiberio, Iolanda F. L. C.
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Prado, Marco Antonio M.
;
Prado, Carla M.
Total Authors: 12
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| Document type: | Journal article |
| Source: | FASEB JOURNAL; v. 31, n. 1, p. 320-332, JAN 2017. |
| Web of Science Citations: | 11 |
| 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: | 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 Opportunities: | Research Projects - Thematic Grants |
| 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 Menegasso |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 14/25689-4 - Effects of cholinergic system in acute and chronic pulmonary inflammation |
| Grantee: | Carla Máximo Prado |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 08/55359-5 - Avaliação da função e da histopatologia pulmonar em modelo experimental de redução da função colinérgica em camundongos geneticamente modificados |
| Grantee: | Carla Máximo Prado |
| Support Opportunities: | Research Grants - Young Investigators Grants |