Author | Lima, Aline C. Brando | |
Author | Machado, Alexandre L. | |
Author | Simon, Patrícia | |
Author | Cavalcante, Moisés M. | |
Author | Rezende, Daniele C. | |
Author | Silva, Gilberto M. Sperandio da | |
Author | Nascimento, Paulo Gustavo B. D. | |
Author | Quintas, Luis E. M. | |
Author | Cunha, Fernando Q. | |
Author | Barreiro, Eliezer J. | |
Author | Lima, Lídia M. | |
Author | Koatz, Vera L. G. | |
Access date | 2019-11-19T12:37:07Z | |
Available date | 2019-11-19T12:37:07Z | |
Document date | 2011 | |
Citation | 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. | pt_BR |
ISSN | 1734-1140 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/37153 | |
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. | pt_BR |
Language | eng | pt_BR |
Publisher | Institute of Pharmcology Polish Academy of Sciences | pt_BR |
Rights | open access | pt_BR |
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 | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/s1734-1140(11)70619-3 | |
Abstract | 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. | pt_BR |
Affilliation | Federal University of Rio de Janeiro. Institute of Medical Biochemistry. Laboratory of Cellular Immunopharmacology. Rio de Janeiro, RJ, Brazil. | pt_BR |
Affilliation | Federal University of Rio de Janeiro. Institute of Medical Biochemistry. Laboratory of Cellular Immunopharmacology. Rio de Janeiro, RJ, Brazil. | pt_BR |
Affilliation | Federal University of Rio de Janeiro. Institute of Medical Biochemistry. Laboratory of Cellular Immunopharmacology. Rio de Janeiro, RJ, Brazil. | pt_BR |
Affilliation | Federal University of Rio de Janeiro. Institute of Medical Biochemistry. Laboratory of Cellular Immunopharmacology. Rio de Janeiro, RJ, Brazil. | pt_BR |
Affilliation | Federal University of Rio de Janeiro. Institute of Biomedical Science. Laboratory of Biochemical and Molecular Pharmacology. Rio de Janeiro, RJ, Brazil. | pt_BR |
Affilliation | University of Rio de Janeiro. Faculty of Pharmacy. Laboratory of Evaluation and Synthesis of Bioactive Substance. Rio de Janeiro, RJ, Brazil. | pt_BR |
Affilliation | University of São Paulo. Faculty of Medicine of Ribeirão Preto. Department of Pharmacology. Laboratory of Pain and Inflammation. São Paulo, SP, Brazil. | pt_BR |
Affilliation | Federal University of Rio de Janeiro. Institute of Biomedical Science. Laboratory of Biochemical and Molecular Pharmacology. Rio de Janeiro, RJ, Brazil. | pt_BR |
Affilliation | University of São Paulo. Faculty of Medicine of Ribeirão Preto. Department of Pharmacology. Laboratory of Pain and Inflammation. São Paulo, SP, Brazil. | pt_BR |
Affilliation | University of Rio de Janeiro. Faculty of Pharmacy. Laboratory of Evaluation and Synthesis of Bioactive Substance. Rio de Janeiro, RJ, Brazil. | pt_BR |
Affilliation | University of Rio de Janeiro. Faculty of Pharmacy. Laboratory of Evaluation and Synthesis of Bioactive Substance. Rio de Janeiro, RJ, Brazil. | pt_BR |
Affilliation | Federal University of Rio de Janeiro. Institute of Medical Biochemistry. Laboratory of Cellular Immunopharmacology. Rio de Janeiro, RJ, Brazil. | pt_BR |
Subject | LASSBio-99 | pt_BR |
Subject | TNF-α | pt_BR |
Subject | Lung inflammation | pt_BR |
Subject | P38 mitogen-activated protein kinase | pt_BR |
Subject | Anti-inflammatory drug candidate | pt_BR |