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In vitro effect of nutritional and active Vitamin D on proinflammatory citokynes production via TLR-4 in monocytes of hemodialysis patients

Grant number: 18/17976-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2018
Effective date (End): March 31, 2019
Field of knowledge:Health Sciences - Nutrition
Principal Investigator:Barbara Perez Vogt
Grantee:Camila Zanini Gimenes de Freitas
Home Institution: Faculdade de Ciências da Saúde (FCSA). Universidade do Oeste Paulista (UNOESTE). Presidente Prudente , SP, Brazil

Abstract

Chronic kidney disease (CKD) exhibits systemic inflammation, which is characterized by increased pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-±), interleukin-6 (IL-6), and interferon-gamma (INF-g). Another common disorder in patients with CKD is hypovitaminosis D and / or vitamin D metabolism disorders. It is postulated that hypovitaminosis D favors the activation of inflammatory response in cells of immune system, mainly via Toll Like Receptor 4 (TLR-4), stimulating nuclear factor kappa B (NF-ºB) in pro-inflammatory cytokines transcription. Nutritional interventions are advocated in the attempt to soften and / or abolish the exacerbated inflammatory response. Therefore, the objective of the present project is to evaluate in vitro effect of nutritional and active (calcitriol) vitamin D on proinflammatory cytokines production of monocytes of hemodialysis patients, exploring the TLR-4 and NF-ºB signaling pathways. Individuals with CKD diagnosis regardless etiology undergoing maintenance hemodialysis will be recruited. After collection of blood, monocytes will be incubated for 24 hours in presence or absence of LPS, homologous serum, and in combination with cholecalciferol or calcitriol. Cytokine dosages in the supernatant (TNF ±, IL-6, IL-10) and gene expression of TLR-4 and NF-ºB in the monocytes exposed to the different treatments will be performed.