Beneficial effects of IL-4 and IL-6 on rat neonatal target cardiac cells

Autor(es)

Zogbi, Camila ^[1] ; Oliveira, Nathalia C. ^[1] ; Levy, Debora ^[1] ; Bydlowski, Sergio P. ^[1] ; Bassaneze, Vinicius ^[1] ; Neri, Elida A. ^[1] ; Krieger, Jose E. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Heart Inst InCor, Sch Med, Lab Genet & Mol Cardiol LIM 13, Av Dr Eneas C Aguiar 44, BR-05403000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 JUL 23 2020.
• Citações Web of Science: 0

Resumo

The nature of the early post-natal immune response in rodents appears to influence cardiac regeneration even though the underlying molecules remain poorly understood. Consistent with this idea, we show now significant changes in the expression of immune and cell movement gene pathways in heart samples from 1- and 7-day-old rats with ventricle resection. We then tested whether conditioned media from adult M2 anti-inflammatory macrophages target neonatal cardiac cells to a pro-regenerative like phenotype compared to the M1 pro-inflammatory macrophages. We found that M2 compared to M1 macrophage-conditioned media upregulates neonatal cardiomyocyte proliferation, suppresses myofibroblast-induced differentiation and stimulates endothelial cell tube formation. Using a cytokine array, we selected four candidate cytokine molecules uniquely expressed in M2 macrophage-conditioned media and showed that two of them (IL-4 and IL-6) induce endothelial cell proliferation whilst IL-4 promotes proliferation in neonatal cardiomyocytes and prevents myofibroblast-induced collagen type I secretion. Altogether, we provided evidence that adult M2 macrophage-conditioned media displays a paracrine beneficial pro-regenerative response in target cardiac cells and that IL-4 and IL-6 recapitulate, at least in part, these pleiotropic effects. Further characterization of macrophage immune phenotypes and their secreted molecules may give rise to novel therapeutic approaches for post-natal cardiac repair. (AU)

• Processo FAPESP: 15/50216-5 - Caracterização da população ideal de células cardíacas derivadas de hiPSC para a regeneração cardíaca após infarto do miocárdio
• Beneficiário: José Eduardo Krieger
• Linha de fomento: Auxílio à Pesquisa - Parceria para Inovação Tecnológica - PITE
• Processo FAPESP: 17/17296-0 - Determinação dos exossomos como os responsáveis pelo efeito cardioprotetor parácrino das células-tronco mesenquimais pós-Infarto Agudo do Miocárdio
• Beneficiário: Nathalia Corrêa de Almeida Oliveira
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/07024-3 - Avaliação dos benefícios da terapia celular com uso de copolímeros inteligentes a base de proteínas recombinantes no pós-infarto do miocárdio de ratos adultos
• Beneficiário: Camila Zogbi Nogueira Perez
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/17368-0 - Genômica cardiovascular: mechanismos & novas terapias - CVGen mech2ther
• Beneficiário: José Eduardo Krieger
• Linha de fomento: Auxílio à Pesquisa - Temático