First transcriptomic insight into the reprogramming of human macrophages by levan-type fructans

Peled E., Tornaci S., Zlotver I., Dubnika A., TOKSOY ÖNER E., Sosnik A.

Carbohydrate Polymers, cilt.320, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 320
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.carbpol.2023.121203
  • Dergi Adı: Carbohydrate Polymers
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, Food Science & Technology Abstracts, Veterinary Science Database
  • Anahtar Kelimeler: Classical (M1) and alternative (M2) macrophage activation, Fructan, Halomonas levan, Immunotherapy, Macrophage polarization, RNA-seq
  • Marmara Üniversitesi Adresli: Evet

Özet

Based on stimuli in the biological milieu, macrophages can undergo classical activation into the M1 pro-inflammatory (anti-cancer) phenotype or to the alternatively activated M2 anti-inflammatory one. Drug-free biomaterials have emerged as a new therapeutic strategy to modulate macrophage phenotype. Among them, polysaccharides polarize macrophages to M1 or M2 phenotypes based on the surface receptors they bind. Levan, a fructan, has been proposed as a novel biomaterial though its interaction with macrophages has been scarcely explored. In this study, we investigate the interaction of non-hydrolyzed and hydrolyzed Halomonas levan and its sulfated derivative with human macrophages in vitro. Viability studies show that these levans are cell compatible. In addition, RNA-sequencing analysis reveals the upregulation of pro-inflammatory pathways. These results are in good agreement with real time-quantitative polymerase chain reaction that indicates higher expression levels of C-X-C Motif Chemokine Ligand 8 and interleukin-6 genes and the M2-to-M1 reprogramming of these cells upon levan treatment. Finally, cytokine release studies confirm that hydrolyzed levans increase the secretion of pro-inflammatory cytokines and reprogram IL-4-polarized macrophages to the M1 state. Overall findings indicate that Halomonas levans trigger a classical macrophage activation and pave the way for their application in therapeutic interventions requiring a pro-inflammatory phenotype.