Functional and biochemical study of neutrophils from patients with Rheumatoid Arthritis and its implications in the search for new therapeutic strategies

• Grant number: 13/21331-5
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2014
• Effective date (End): February 28, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Yara Maria Lucisano Valim
• Grantee: Larissa Fávaro Marchi
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Neutrophils or polymorphonuclear (PMN) cells are phagocytic with functions highly potent bactericidal and fungicidal. These cells are able to kill microorganisms through mechanisms independent of oxygen (phagocytosis and degranulation) , and oxygen dependent (production of reactive oxygen species). However, in severe situations of cellular activation , release of large cytotoxic molecules may cause deleterious effects in tissues such as occurs in Rheumatoid Arthritis (RA), autoimmune disease mainly characterized by synovial hyperplasia , swelling , pain, cellular infiltration containing predominately PMNs and joint destruction . Moreover, the activation of PMNs may be mediated by Fc³R and complement receptors (CR) present in the membrane of these cells through interaction with immune complexes (IC) inside the inflammatory micro-environment. Given this, an attractive approach for RA treatment is the modulation of the effectors functions of PMNs. In this sense, the use of natural compounds have been extensively investigated and among them we highlight the flavonoid metabolites that appear as promising showing antioxidant and immunomodulatory activities. Previous studies in our laboratory with 17 different flavonoid structures showed that some selected substances showed a significant antioxidant activity, dependent on the concentration and structure on PMNs. Continuing research, started an integrated study that aim to understand a planned manner the (s) mechanism (s) of action of flavonoids on the oxidative metabolism of PMN stimulated by immune complexes formed with the antibody in the absence or presence complement. Thus, to better understand the role of these flavonoids in modulating PMNs and the recognition of these natural substances as a potential therapeutic agent in the treatment of RA, this project aims to assess the modulatory action of galangin and quercetin on some important effector functions of PMNs (such as production of reactive oxygen species and chemotaxis ) , and to evaluate the apoptosis of these cells , since this feature is important to maintain homeostasis.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALBIERO, LUCINEIA REUSE; DE ANDRADE, MICASSIO FERNANDES; MARCHI, LARISSA FAVARO; LANDI-LIBRANDI, ANA PAULA; GARCIA DE FIGUEIREDO-RINHEL, ANDREA SILVA; CARVALHO, CAMILA ANDRESSA; KABEYA, LUCIANA MARIKO; RIBEIRO DE OLIVEIRA, RENE DONIZETI; CALEIRO SEIXAS AZZOLINI, ANA ELISA; PUPO, MONICA TALLARICO; et al. Immunomodulating action of the 3-phenylcoumarin derivative 6,7-dihydroxy-3-[3 `,4 `-methylenedioxyphenyl]-coumarin in neutrophils from patients with rheumatoid arthritis and in rats with acute joint inflammation. Inflammation Research, v. 69, n. 1, NOV 2019. (12/23541-4, 13/21331-5, 13/20810-7)