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

Autor: Zogbi C; Lab Genetics & Mol Cardiology/LIM 13, Heart Institute (InCor), University of São Paulo Medical School, Av Dr Eneas C Aguiar 44, Sao Paulo, SP, 05403-000, Brazil., Oliveira NC; Lab Genetics & Mol Cardiology/LIM 13, Heart Institute (InCor), University of São Paulo Medical School, Av Dr Eneas C Aguiar 44, Sao Paulo, SP, 05403-000, Brazil., Levy D; Lab Genetics & Mol Cardiology/LIM 13, Heart Institute (InCor), University of São Paulo Medical School, Av Dr Eneas C Aguiar 44, Sao Paulo, SP, 05403-000, Brazil., Bydlowski SP; Lab Genetics & Mol Cardiology/LIM 13, Heart Institute (InCor), University of São Paulo Medical School, Av Dr Eneas C Aguiar 44, Sao Paulo, SP, 05403-000, Brazil., Bassaneze V; Lab Genetics & Mol Cardiology/LIM 13, Heart Institute (InCor), University of São Paulo Medical School, Av Dr Eneas C Aguiar 44, Sao Paulo, SP, 05403-000, Brazil., Neri EA; Lab Genetics & Mol Cardiology/LIM 13, Heart Institute (InCor), University of São Paulo Medical School, Av Dr Eneas C Aguiar 44, Sao Paulo, SP, 05403-000, Brazil., Krieger JE; Lab Genetics & Mol Cardiology/LIM 13, Heart Institute (InCor), University of São Paulo Medical School, Av Dr Eneas C Aguiar 44, Sao Paulo, SP, 05403-000, Brazil. krieger@incor.usp.br.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Jul 23; Vol. 10 (1), pp. 12350. Date of Electronic Publication: 2020 Jul 23.
DOI: 10.1038/s41598-020-69413-0
Abstrakt: 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.
Databáze: MEDLINE
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