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

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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 ; Emery, Flavio da Silva ; Lucisano-Valim, Yara Maria

• Tipo de documento: Artigo Científico
• Fonte: Inflammation Research; v. 69, n. 1, p. 16-pg., 2019-11-30.

Resumo

Objective To examine whether free (3-PD-5(free)) and/or liposomal (3-PD-5(lipo)) 6,7-dihydroxy-3-[3 ',4 '-methylenedioxyphenyl]-coumarin (3-PD-5) (1) modulate the effector functions of neutrophils from patients with rheumatoid arthritis under remission (i-RA) and with active disease (a-RA), in vitro; and (2) exert anti-inflammatory effect in a rat model of zymosan-induced acute joint inflammation. Methods and results Incorporation of 3-PD-5 into unilamellar liposomes of soya phosphatidylcholine and cholesterol was efficient (57.5 +/- 7.9%) and yielded vesicles with low diameter (133.7 +/- 18.4 nm), polydispersity index (0.39 +/- 0.06), and zeta potential (- 1.22 +/- 0.34 mV). 3-PD-5(free) (1 mu M) and 3-PD-5(lipo) (3 mu M) equally suppressed elastase release and reactive oxygen species generation in neutrophils from healthy subjects and i-RA and a-RA patients, stimulated with immune complexes. 3-PD-5(free) (20 mu M) suppressed the release of neutrophil extracellular traps and chemotaxis in vitro, without clear signs of cytotoxicity. 3-PD-5(lipo) (1.5 mg/kg, i.p.) diminished joint edema and synovial infiltration of total leukocytes and neutrophils, without changing the synovial levels of TNF-alpha, IL-1 beta, and IL-6. Conclusion Altogether, the results reported herein indicate that 3-PD-5 is a promising modulator of the early stages of acute joint inflammation that can help to diminish not only excessive neutrophil infiltration in the synovia but also neutrophil activation and its outcomes in RA patients. (AU)

• Processo FAPESP: 13/21331-5 - Estudo bioquímico e funcional de neutrófilos de pacientes com Artrite Reumatóide e suas implicações na busca de novas estratégias terapêuticas
• Beneficiário: Larissa Fávaro Marchi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/20810-7 - Estudo sistemático dos mecanismos moleculares envolvidos na inibição do metabolismo oxidativo de neutrófilos exercida pela Baccharis dracunculifolia, derivado 3-fenilcumarinicos e 3,5,7-triidroxiflavona: implicação em uma nova abordagem terapêutica da AR
• Beneficiário: Yara Maria Lucisano Valim
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/23541-4 - Avaliação in vitro dos efeitos antioxidante e anti-inflamatório de derivados 3-fenilcumarínicos em neutrófilos humanos estimulados e em modelo animal de artrite
• Beneficiário: Micássio Fernandes de Andrade
• Modalidade de apoio: Bolsas no Brasil - Doutorado