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INHIBITION OF GAMMA-SECRETASE ACTIVITY WITHOUT INTERFERING IN NOTCH SIGNALLING DECREASES INFLAMMATORY RESPONSE IN PATIENTS WITH CUTANEOUS LEISHMANIASIS
Nascimento, Maurício T. et al. | Date Issued: 2021
Author
Nascimento, Maurício T.
Franca, Mônica
Carvalho, Augusto M.
Amorim, Camila F.
Peixoto, Fábio
Beiting, Daniel
Scott, Phillip
Carvalho, Edgar Marcelino
Carvalho, Lucas Pedreira
Affilliation
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil / Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil.
Universidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
University of Pennsylvania. Department of Pathobiology. Philadelphia, PA, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
University of Pennsylvania. Department of Pathobiology. Philadelphia, PA, USA.
University of Pennsylvania. Department of Pathobiology. Philadelphia, PA, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil / Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil / Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brasil.
Abstract
Cutaneous leishmaniasis (CL) patients present an exacerbated inflammatory response associated with tissue damage and ulcer development. Increasing numbers of patients have exhibited treatment failure, which remains not well understood. We hypothesized that adjuvant anti-inflammatory therapy would benefit CL patients. The aim of the present study was to investigate the contribution of Notch signalling and gamma-secretase activity to the inflammatory response observed in CL patients. Notch signalling is a molecular signalling pathway conserved among animal species. Gamma-secretase forms a complex of proteins that, among other pathways, modulates Notch signalling and immune response. We found that Notch 1 cell receptor signalling protects against the pathologic inflammatory response, and JLK6, a gamma-secretase inhibitor that does not interfere with Notch signalling, was shown to decrease the in-vitro inflammatory response in CL. Our data suggest that JLK6 may serve as an adjuvant treatment for CL patients.
Keywords in Portuguese
Leishmaniose cutânea
Falhas de tratamento
Citocinas
Resposta inflamatória
Leishmania braziliensis
 
Keywords
Cutaneous leishmaniasis
Notch signalling
Cytokines
Inflammatory response
Leishmania braziliensis
 
Publisher
Taylor & Francis Open Access
Citation
NASCIMENTO, Maurício T. et al. Inhibition of gamma-secretase activity without interfering in Notch signalling decreases inflammatory response in patients with cutaneous leishmaniasis. Emerging Microbes and Infections, v. 10, n. 1, 16 June 2021.
DOI
10.1080/22221751.2021.1932608
ISSN
2222-1751