AUTHOR=Anfossi Renatto , Vivar Raúl , Ayala Pedro , González-Herrera Fabiola , Espinoza-Pérez Claudio , Osorio José Miguel , Román-Torres Mauricio , Bolívar Samir , Díaz-Araya Guillermo 

TITLE=Interferon-β decreases LPS-induced neutrophil recruitment to cardiac fibroblasts

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1122408

DOI=10.3389/fcell.2023.1122408

ISSN=2296-634X

ABSTRACT=Cardiac fibroblasts (CF) have been recognized as sentinel cells due to their regulatory functions on the inflammatory infiltrate cells in damaged tissues. CF expresses TLR4 and secretes pro-inflammatory mediators; it also secretes, and responds to interferon-β (IFN-β), which has been shown to modulate the inflammatory response of CF. We have shown that CF interacts with immune cells; however, CF interaction with neutrophils has not been studied in depth. The effects of lipopolysaccharide (LPS) and/or IFN-β on CF-neutrophil interaction are poorly understood. CF isolated from adult Sprague-Dawley rats were treated with LPS in the presence/absence of IFN-β. IL-8 secretion, ICAM-1 and VCAM-1 expression, recruitment of neutrophils, and the consequences of CF-neutrophil interaction on MMPs activity were also evaluated. The results show that LPS induced an increase in IL-8 expression and secretion; and in ICAM-1 and VCAM-1 expression. These effects of LPS were blocked by TAK-242. Pretreatment of CF with IFN-β prevented these effects of LPS on CF. In LPS-treated CF, neutrophil recruitment was increased and the pre-treatment with IFN-β prevented LPS effects. The anti-inflammatory effects of IFN-β were blocked by ruxolitinib, a JAK inhibitor, suggesting that the effect of IFN-β is mediated via JAK. Analysis of zymograms of the culture medium from CF alone, treated CF co-cultured with adherent neutrophils, showed that MMP2 was mainly derived from CF, whereas MMP9 could be derived from neutrophils. In CF alone, both LPS and IFN-β treatment increased the secretion of MMP2. CF alone showed low MMP9 activity, and LPS or IFN-β did not change MMP9 activities. When CF were previously pre-treated with LPS, IFN-β and IFN-β + LPS and then co-cultured with neutrophils, an increase in MMP2 was observed. In CF co-cultured with neutrophils, an increase in MMP9 activity was observed, although these effects were less pronounced in CF pre-treated with IFN-β, where a decrease in MMP9 was observed with respect to unstimulated CF.Conclusions: . Our results highlight that interaction between CF and neutrophils could play a key role in modifying the extracellular matrix by altering MMPs activity.