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Immunomodulatory action and epigenetic and transcriptional evaluation of natural killer cells submitted to Bothrops moojeni L-amino acid oxidase enzyme and to Bothrops jararacussu BthTX-I phospholipase

Grant number: 15/26901-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2016
Effective date (End): December 31, 2016
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Suely Vilela
Grantee:Murilo Racy Soares
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis, AP.TEM

Abstract

The L-amino acid oxidases (LAAOs) flavoenzymes and the phospholipases have a broad spectrum of biological and pharmacological activities. The aim of this study is to characterize and elucidate the immunomodulatory activity and the transcriptional and epigenetic effects of LAAO isolated from Bothrops moojeni and the phospholipase BthTX-I isolated from Bothrops jararacussu produces on NK cells (natural killer) cultured in vitro. NK cells constitute a crucial lineage of effector lymphocytes to innate immune system of humans, which are directly involved in the control of tumorigenesis, microbial infection and are intrinsically involved in the cellular interaction with dendritic cells, macrophages, T cells and endothelial cells, and also develop significant modulatory role, limiting or exacerbating the immune response. NK cells produce, among others, the cytokines IFN-c, IFN-± and IFN-², TNF-± and IL-6 which are involved in the recruitment and activation of other immune effector cells. Therefore, the phenotypic characterization along the quantification of cytokines produced by these cells, will show how LAAO of B. moojeni and BthTX-I of B. jararacussu could modulate the effector functions of NK cells. In addition, the global epigenetic analysis of the NK cells and epigenetic analysis of the promoter regions along with the genomic and transcriptional analysis of genes TNF, IL6 and IFNG, will assist and provide clues regarding the status, the pattern and genetic behavior, and immune cell environment induced. Thus, the evaluation of the NK cell response pattern when in contact with the toxins BthTX and LAAO can contribute in elucidating the immunological mechanisms involved and further assist in understanding the biological activity of these enzymes. (AU)