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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01368

IFN-β plays both pro- and anti-inflammatory roles in the rat cardiac fibroblast through differential STAT protein activation

Samir Bolivar González1, Renatto Anfossi1, Raul Vivar2, Claudio Humeres1, Pía Boza1, Claudia Muñoz1, Viviana Pardo-Jimenez1, Francisco Olivares-Silva1 and  Guillermo Diaz-Araya1*
  • 1Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Chile
  • 2Universidad de Chile, Chile

Cardiac fibroblasts (CF) contribute to theinflammatory response to tissue damage, secreting both pro- and anti-inflammatory cytokines and chemokines. Interferon beta (IFN-β) induces the phosphorylation of signal transducer and activator of transcription(STAT) proteins through the activation of its own receptor, modulating the secretion of cytokines and chemokines which regulate inflammation. However, the role of IFN-β and STAT proteins in modulating the inflammatory response of CF remains unknown.
CF were isolated from adult male rats and subsequently stimulated with IFN-β to evaluate the participation of STAT proteins in secreting chemokines, cytokines, cell adhesion proteins expression and in their capacity to recruit neutrophils. In addition, in CF in which the TRL4 receptor was pre-activated, the effect of INF- on the aforementioned responses was also evaluated.
CF stimulation with IFN-β showed an increase in STAT1, STAT2, and STAT3 phosphorylation. IFN-β stimulation through STAT1 activation increased proinflammatory chemokines MCP-1 and IP-10 secretion, whereas IFN-β induced activation of STAT3 increased cytokine secretion of anti-inflammatory IL-10. Moreover, in TLR4-activated CF, IFN-β through STAT2 and/or STAT3, produced an anti-inflammatory effect, reducing pro-IL-1, TNF-α, IL-6, MCP-1, and IP-10 secretion; and decreasing neutrophil recruitment by decreasing ICAM-1 and VCAM-1 expression.
Altogether, our results indicate that IFN-β exerts both pro-inflammatory and anti-inflammatory effects in non-stimulated CF, through differential activation of STAT proteins. When CF were previously treated with an inflammatory agent such as TLR-4 activation, IFN-β effects were predominantly anti-inflammatory.

Keywords: IFN-β (interferon β), cardiac fibroblast, STAT, proinflammatory, Anti-infammatory

Received: 25 Aug 2018; Accepted: 07 Nov 2018.

Edited by:

Lei Xi, School of Medicine, Virginia Commonwealth University, United States

Reviewed by:

Francisco Villarreal, University of California, San Diego, United States
Zhi-Qing Zhao, Mercer University, United States  

Copyright: © 2018 Bolivar González, Anfossi, Vivar, Humeres, Boza, Muñoz, Pardo-Jimenez, Olivares-Silva and Diaz-Araya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Guillermo Diaz-Araya, Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Santiago Metropolitan Region (RM), Chile, gadiaz@ciq.uchile.cl