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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 JUL 23 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 15/50216-5 - Characterization of the optimal hiPSC-derived cardiac cell population for heart regeneration after myocardial infarction
• Grantee: José Eduardo Krieger
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE
• FAPESP's process: 17/17296-0 - Mesenchymal stem cells-derived exosomes as paracrine effectors for cardioprotection after Acute Myocardial Infarction
• Grantee: Nathalia Corrêa de Almeida Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/07024-3 - Evaluation of cell therapy benefits based on smart copolymers combined to recombinant proteins after myocardial infarction in adult rats
• Grantee: Camila Zogbi Nogueira Perez
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther
• Grantee: José Eduardo Krieger
• Support Opportunities: Research Projects - Thematic Grants