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

dc.creatorLima, Aline C. Brando
dc.creatorMachado, Alexandre L.
dc.creatorSimon, Patrícia
dc.creatorCavalcante, Moisés M.
dc.creatorRezende, Daniele C.
dc.creatorSilva, Gilberto M. Sperandio da
dc.creatorNascimento, Paulo Gustavo B. D.
dc.creatorQuintas, Luis E. M.
dc.creatorCunha, Fernando Q.
dc.creatorBarreiro, Eliezer J.
dc.creatorLima, Lídia M.
dc.creatorKoatz, Vera L. G.
dc.date2019-11-19T12:37:07Z
dc.date2019-11-19T12:37:07Z
dc.date2011
dc.date.accessioned2023-09-26T20:41:37Z
dc.date.available2023-09-26T20:41:37Z
dc.identifierLIMA, 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.
dc.identifier1734-1140
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/37153
dc.identifier10.1016/s1734-1140(11)70619-3
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8862129
dc.descriptionGilberto 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.
dc.descriptionWe 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherInstitute of Pharmcology Polish Academy of Sciences
dc.rightsopen access
dc.subjectLASSBio-99
dc.subjectTNF-α
dc.subjectLung inflammation
dc.subjectP38 mitogen-activated protein kinase
dc.subjectAnti-inflammatory drug candidate
dc.titleAnti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation
dc.typeArticle


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