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.

Details

Title
Inhibition of gamma-secretase activity without interfering in Notch signalling decreases inflammatory response in patients with cutaneous leishmaniasis
Author
Nascimento, Maurício T 1   VIAFID ORCID Logo  ; Franca, Mônica 2   VIAFID ORCID Logo  ; Carvalho, Augusto M 3   VIAFID ORCID Logo  ; Amorim, Camila F 4   VIAFID ORCID Logo  ; Peixoto, Fábio 3   VIAFID ORCID Logo  ; Beiting, Daniel 4   VIAFID ORCID Logo  ; Scott, Phillip 4   VIAFID ORCID Logo  ; Carvalho, Edgar M 5   VIAFID ORCID Logo  ; Carvalho, Lucas P 6   VIAFID ORCID Logo 

1  Laboratório de Pesquisas Clínicas; Instituto Gonçalo Moniz, FIOCRUZ, Salvador, Brazil; Serviço de Imunologia, Complexo Hospitalar Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil 
2  Instituto de Ciências e Saúde Universidade Federal da Bahia, Salvador, Brazil 
3  Laboratório de Pesquisas Clínicas; Instituto Gonçalo Moniz, FIOCRUZ, Salvador, Brazil 
4  Department of Pathobiology, University of Pennsylvania, Philadelphia, PA, USA 
5  Laboratório de Pesquisas Clínicas; Instituto Gonçalo Moniz, FIOCRUZ, Salvador, Brazil; Serviço de Imunologia, Complexo Hospitalar Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil; Instituto Nacional de Ciências e Tecnologia-Doenças Tropicais, Salvador, Brazil 
6  Laboratório de Pesquisas Clínicas; Instituto Gonçalo Moniz, FIOCRUZ, Salvador, Brazil; Serviço de Imunologia, Complexo Hospitalar Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil; Instituto de Ciências e Saúde Universidade Federal da Bahia, Salvador, Brazil; Instituto Nacional de Ciências e Tecnologia-Doenças Tropicais, Salvador, Brazil 
Pages
1219-1226
Publication year
2021
Publication date
Dec 2021
Publisher
Taylor & Francis Ltd.
e-ISSN
22221751
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/22221751.2021.1932608
ProQuest document ID
3190429815
Copyright
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.