Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2011 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/37153 |
Resumo: | Gilberto M. Sperandio da Silva. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento. |
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Lima, Aline C. BrandoMachado, Alexandre L.Simon, PatríciaCavalcante, Moisés M.Rezende, Daniele C.Silva, Gilberto M. Sperandio daNascimento, Paulo Gustavo B. D.Quintas, Luis E. M.Cunha, Fernando Q.Barreiro, Eliezer J.Lima, Lídia M.Koatz, Vera L. G.2019-11-19T12:37:07Z2019-11-19T12:37:07Z2011LIMA, Aline C. Brando et al. Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation. Pharmacological Reports, v. 63, p. 1029-1039, 2011.1734-1140https://www.arca.fiocruz.br/handle/icict/3715310.1016/s1734-1140(11)70619-3Gilberto M. Sperandio da Silva. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.Federal University of Rio de Janeiro. Institute of Medical Biochemistry. Laboratory of Cellular Immunopharmacology. Rio de Janeiro, RJ, Brazil.Federal University of Rio de Janeiro. Institute of Medical Biochemistry. Laboratory of Cellular Immunopharmacology. Rio de Janeiro, RJ, Brazil.Federal University of Rio de Janeiro. Institute of Medical Biochemistry. Laboratory of Cellular Immunopharmacology. Rio de Janeiro, RJ, Brazil.Federal University of Rio de Janeiro. Institute of Medical Biochemistry. Laboratory of Cellular Immunopharmacology. Rio de Janeiro, RJ, Brazil.Federal University of Rio de Janeiro. Institute of Biomedical Science. Laboratory of Biochemical and Molecular Pharmacology. Rio de Janeiro, RJ, Brazil.University of Rio de Janeiro. Faculty of Pharmacy. Laboratory of Evaluation and Synthesis of Bioactive Substance. Rio de Janeiro, RJ, Brazil.University of São Paulo. Faculty of Medicine of Ribeirão Preto. Department of Pharmacology. Laboratory of Pain and Inflammation. São Paulo, SP, Brazil.Federal University of Rio de Janeiro. Institute of Biomedical Science. Laboratory of Biochemical and Molecular Pharmacology. Rio de Janeiro, RJ, Brazil.University of São Paulo. Faculty of Medicine of Ribeirão Preto. Department of Pharmacology. Laboratory of Pain and Inflammation. São Paulo, SP, Brazil.University of Rio de Janeiro. Faculty of Pharmacy. Laboratory of Evaluation and Synthesis of Bioactive Substance. Rio de Janeiro, RJ, Brazil.University of Rio de Janeiro. Faculty of Pharmacy. Laboratory of Evaluation and Synthesis of Bioactive Substance. Rio de Janeiro, RJ, Brazil.Federal University of Rio de Janeiro. Institute of Medical Biochemistry. Laboratory of Cellular Immunopharmacology. Rio de Janeiro, RJ, Brazil.We investigated the effects of LASSBio-998 (L-998), a compound designed to be a p38 MAPK (mitogen-activated protein kinase) inhibitor, on lipopolysaccharide (LPS)-induced acute lung inflammation in vivo. BALB/c mice were challenged with aerosolized LPS inhalation (0.5 mg/ml) 4 h after oral administration of L-998. Three hours after LPS inhalation, bronchoalveolar lavage fluid was obtained to measure the levels of the proinflammatory cytokines TNF-α (tumor necrosis factor-α) and IL-1 (interleukin-1) and the chemokines MCP-1 (monocyte chemoattractant protein-1) and KC (keratinocyte chemoattractant). In addition, neutrophil infiltration and p38 MAPK phosphorylation was measured. L-998 inhibited LPS-induced production of TNF-α and IL-1β and did not alter KC and MCP-1 levels. Furthermore, L-998 also significantly decreased neutrophil accumulation in lung tissues. As expected, L-998 diminished p38 MAPK phosphorylation and reduced acute lung inflammation. Inhibition of p38 MAPK phosphorylation by L-998 was also demonstrated in LPS-challenged murine C57BL/6 peritoneal macrophages in vitro, with concentration-dependent effects. L-998 suppressed LPS-induced lung inflammation, most likely by inhibition of the cytokine-p38 MAPK pathway, and we postulate that L-998 could be a clinically relevant anti-inflammatory drug candidate.engInstitute of Pharmcology Polish Academy of SciencesAnti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLASSBio-99TNF-αLung inflammationP38 mitogen-activated protein kinaseAnti-inflammatory drug candidateinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/37153/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINALve_Lima_Aline_etal_INI_2011.pdfve_Lima_Aline_etal_INI_2011.pdfapplication/pdf1143352https://www.arca.fiocruz.br/bitstream/icict/37153/2/ve_Lima_Aline_etal_INI_2011.pdf420752de273c098969f6ab7189ebcb33MD52TEXTve_Lima_Aline_etal_INI_2011.pdf.txtve_Lima_Aline_etal_INI_2011.pdf.txtExtracted texttext/plain41578https://www.arca.fiocruz.br/bitstream/icict/37153/3/ve_Lima_Aline_etal_INI_2011.pdf.txt41ddd5203abaad1b0dae9ad52a46c01aMD53icict/371532019-11-20 02:00:32.439oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-11-20T05:00:32Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation |
| title |
Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation |
| spellingShingle |
Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation Lima, Aline C. Brando LASSBio-99 TNF-α Lung inflammation P38 mitogen-activated protein kinase Anti-inflammatory drug candidate |
| title_short |
Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation |
| title_full |
Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation |
| title_fullStr |
Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation |
| title_full_unstemmed |
Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation |
| title_sort |
Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation |
| author |
Lima, Aline C. Brando |
| author_facet |
Lima, Aline C. Brando Machado, Alexandre L. Simon, Patrícia Cavalcante, Moisés M. Rezende, Daniele C. Silva, Gilberto M. Sperandio da Nascimento, Paulo Gustavo B. D. Quintas, Luis E. M. Cunha, Fernando Q. Barreiro, Eliezer J. Lima, Lídia M. Koatz, Vera L. G. |
| author_role |
author |
| author2 |
Machado, Alexandre L. Simon, Patrícia Cavalcante, Moisés M. Rezende, Daniele C. Silva, Gilberto M. Sperandio da Nascimento, Paulo Gustavo B. D. Quintas, Luis E. M. Cunha, Fernando Q. Barreiro, Eliezer J. Lima, Lídia M. Koatz, Vera L. G. |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Lima, Aline C. Brando Machado, Alexandre L. Simon, Patrícia Cavalcante, Moisés M. Rezende, Daniele C. Silva, Gilberto M. Sperandio da Nascimento, Paulo Gustavo B. D. Quintas, Luis E. M. Cunha, Fernando Q. Barreiro, Eliezer J. Lima, Lídia M. Koatz, Vera L. G. |
| dc.subject.en.pt_BR.fl_str_mv |
LASSBio-99 TNF-α Lung inflammation P38 mitogen-activated protein kinase Anti-inflammatory drug candidate |
| topic |
LASSBio-99 TNF-α Lung inflammation P38 mitogen-activated protein kinase Anti-inflammatory drug candidate |
| description |
Gilberto M. Sperandio da Silva. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento. |
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2011 |
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2011 |
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2019-11-19T12:37:07Z |
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2019-11-19T12:37:07Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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LIMA, Aline C. Brando et al. Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation. Pharmacological Reports, v. 63, p. 1029-1039, 2011. |
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https://www.arca.fiocruz.br/handle/icict/37153 |
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1734-1140 |
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10.1016/s1734-1140(11)70619-3 |
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LIMA, Aline C. Brando et al. Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation. Pharmacological Reports, v. 63, p. 1029-1039, 2011. 1734-1140 10.1016/s1734-1140(11)70619-3 |
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Institute of Pharmcology Polish Academy of Sciences |
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