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Evaluation of the crotamine action in mononuclear cells and its potential use in the modulation of inflammatory pathways

Grant number: 16/25442-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2017
Effective date (End): December 31, 2017
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Irina Kerkis
Grantee:Aline Cristina Miranda Marinho Costa
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Crotamine is a basic polypeptide found in the venom of Crotalus durissus terrificus. Crotamine is of great biotechnological interest since it is classified as a cell penetrating peptide (CPP), this feature is directed mainly to cells in proliferation, what proposes that tumour cells could be a target of it. Recently it was addressed in the literature, a new activity of crotamine in the stimulus of the phagocytic capacity in macrophages, what suggests its potential role in the modulation of immune system. It is known that crotamine has an inhibitory action under the potassium channel voltage-gated potassium channel Kv1.3, which is greatly expressed in cells with inflammatory potential. Thus, it is proposed the evaluation of the action of crotamine in mononuclear cells through the analysis of cell proliferation, inflammatory proteins, quantification of cytokines and evaluation of the calcium and potassium flux. By silencing the gene KCNA3 (gene that codifies Kv1.3), it is intended the verification whether the possible action of crotamine in the modulation of pathways related to the inflammatory process is dependent of this channel. In view of this, the proposed project suggests for the first time new study models to verify this potential and, furthermore, it proposes the utilization of crotamine as a study tool in order to understand these pathways, which are associated with the pathology of many diseases with inflammatory diseases. (AU)