Galectin-1 Facilitates Macrophage Reprogramming and Resolution of Inflammation Through IFN-β

Hiba Yaseen, Sergei Butenko, Irina Polishuk-Zotkin, Sagie Schif-Zuck, Juan Manuel Pérez-Sáez, Gabriel Adrian Rabinovich, Amiram Ariel

Research output: Contribution to journalArticlepeer-review

Abstract

During the resolution of acute inflammation, macrophages undergo reprogramming from pro-inflammatory, to anti-inflammatory/reparative, and eventually to pro-resolving macrophages. Galectin-1 (Gal-1) is a bona fide pro-resolving lectin while interferon β (IFN-β) was recently shown to facilitate macrophage reprogramming and resolution of inflammation. In this study, we found Gal-1null mice exhibit a hyperinflammatory phenotype during the resolution of zymosan A-induced peritonitis but not during the early inflammatory response. This phenotype was characterized by reduced macrophage numbers, increased secretion of pro-inflammatory cytokines, such as interleukin-12 (IL-12), and reduced secretion of anti-inflammatory cytokines, such as interleukin-10 (IL-10). In addition, we found a delayed expression of the pro-resolving enzyme 12/15-lipoxygenase in macrophages and heightened levels of the inflammatory protease proteinase-3 (PR3) in peritoneal fluids from Gal-1null mice. Moreover, we observed sex-dependent differences in the inflammatory profile of Gal-1null mice. Notably, we found that IFN-β levels were reduced in resolution-phase exudates from Gal-1null mice. Administration of IFN-β in vivo or ex vivo treatment was able to rescue, at least in part, the hyperinflammatory profile of Gal-1null mice. In particular, IFN-β recovered a subset of F4/80+GR-1+ macrophages, restored IL-12 and IL-10 secretion from macrophages to WT values and diminished abnormal peritoneal PR3 levels in Gal-1null mice. In conclusion, our results revealed a new Gal-1-IFN-β axis that facilitates the resolution of inflammation and might restrain uncontrolled inflammatory disorders.

Original languageEnglish
Article number901
JournalFrontiers in Pharmacology
Volume11
DOIs
StatePublished - 17 Jun 2020

Bibliographical note

Publisher Copyright:
© Copyright © 2020 Yaseen, Butenko, Polishuk-Zotkin, Schif-Zuck, Pérez-Sáez, Rabinovich and Ariel.

Keywords

  • galectin-1
  • interferon-β
  • macrophage reprogramming
  • proteinase 3
  • resolution of inflammation

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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