Author | Almeida, Lucas Frederico de | |
Author | Silva, Juliana Almeida | |
Author | Andrade, Viviane Magalhães | |
Author | Machado, Paulo Roberto Lima | |
Author | Jamieson, Sarra E | |
Author | Carvalho Filho, Edgar Marcelino | |
Author | Blackwell, Jenefer M | |
Author | Castellucci, Léa Cristina de Carvalho | |
Access date | 2018-02-20T17:52:29Z | |
Available date | 2018-02-20T17:52:29Z | |
Document date | 2017 | |
Citation | ALMEIDA, L. F. et al. Analysis of expression of FLI1 and MMP1 in American cutaneous leishmaniasis caused by Leishmania braziliensis infection. Infection, Genetics and Evolution, v. 49, p. 212–220, 2017. | pt_BR |
ISSN | 1567-1348 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/24893 | |
Description | CARVALHOI FILHO, Edgar Marcelino de. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. | pt_BR |
Sponsorship | theNIH Grant AI 30639 and CNPq/INCT. | pt_BR |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Leishmaniose | pt_BR |
Subject in Portuguese | FLI1 | pt_BR |
Subject in Portuguese | MMP1 | pt_BR |
Subject in Portuguese | IL-6 | pt_BR |
Subject in Portuguese | Lesões cutâneas | pt_BR |
Subject in Portuguese | Macrófagos | pt_BR |
Title | Analysis of expression of FLI1 and MMP1 in American cutaneous leishmaniasis caused by Leishmania braziliensis infection | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.meegid.2017.01.018 | |
Abstract | FLI1 (Friend leukemia virus integration 1) and IL6 (interleukin 6; IL-6) are associated with Leishmania braziliensis susceptibility. Cutaneous lesions show exaggerated matrix metalloproteinase 1 (MMP1). In other skin diseases, FLI1 promoter methylation reduces FLI1 expression, and low FLI1 down-regulates MMP1. IL-6 increases FLI1 expression. We hypothesized that epigenetic regulation of FLI1 in cutaneous leishmaniasis, together with IL-6, might determine MMP1 expression. While generally low (<10%), percent FLI1 promoter methylation was lower (P=0.001) in lesion biopsies than normal skin. Contrary to expectation, a strong positive correlation occurred between FLI1 methylation and gene expression in lesions (r=0.98, P=0.0005) and in IL-6-treated L. braziliensis-infected macrophages (r=0.99, P=0.0004). In silico analysis of the FLI1 promoter revealed co-occurring active H3K27ac and repressive DNA methylation marks to enhance gene expression. FLI1 expression was enhanced between 3 and 24hour post infection in untreated (P=0.0002) and IL-6-treated (P=0.028) macrophages. MMP1 was enhanced in lesion biopsies (P=0.0002), induced (P=0.007) in infected macrophages, but strongly inhibited by IL-6. No correlations occurred between FLI1 and MMP1 expression in lesions or infected macrophages (with/without IL-6). We conclude that MMP1 is regulated by factors other than FLI1, and that the influence of IL-6 on MMP1 was independent of its effect on FLI1. | pt_BR |
Affilliation | Federal University of Bahia. National Institute of Science and Technology in Tropical Diseases. Salvador, BA, Brazil / Federal University of Bahia. Post-graduation in Health Sciences. Salvador, BA, Brazil | pt_BR |
Affilliation | Federal University of Bahia. National Institute of Science and Technology in Tropical Diseases. Salvador, BA, Brazil / Federal University of Bahia. Post-graduation in Health Sciences. Salvador, BA, Brazil | pt_BR |
Affilliation | Federal University of Bahia. National Institute of Science and Technology in Tropical Diseases. Salvador, BA, Brazil / Federal University of Bahia. Post-graduation in Health Sciences. Salvador, BA, Brazil | pt_BR |
Affilliation | Federal University of Bahia. National Institute of Science and Technology in Tropical Diseases. Salvador, BA, Brazil | pt_BR |
Affilliation | The University of Western Australia.Telethon Kids Institute. Subiaco, Western Australia, Australia | pt_BR |
Affilliation | Federal University of Bahia. National Institute of Science and Technology in Tropical Diseases. Salvador, BA, Brazil | pt_BR |
Affilliation | The University of Western Australia.Telethon Kids Institute. Subiaco, Western Australia, Australia / University of Cambridge. Cambridge Institute for Medical Research. Department of Pathology. Cambridge, UK | pt_BR |
Affilliation | Federal University of Bahia. National Institute of Science and Technology in Tropical Diseases. Salvador, BA, Brazil | pt_BR |
Subject | Leishmaniasis | pt_BR |
Subject | FLI1 | pt_BR |
Subject | MMP1 | pt_BR |
Subject | IL-6 | pt_BR |
Subject | Cutaneous lesions | pt_BR |
Subject | Macrophages | pt_BR |