Particulate β-glucan induces TNF-α production in wound macrophages via a redox-sensitive NF-κβ-dependent pathway.

Abstract

Glucans are known to promote wound repair. Noncellulosic β-glucans are recognized as potent immunological activators. β-Glucans are generally safe and are known to attenuate the rate of postoperative infection. Glyc101 is a particulate β-glucan isolated from Saccharomyces cerevisiae. In this study, the hypothesis that Glyc101 regulates wound macrophage function was tested. Glyc101 induced tumor necrosis factor (TNF) α transcription in macrophages isolated from murine wound site. Multiplex assay identified interleukin (IL)-10 and TNFα as two cytokines that are induced by Glyc101 in human blood monocyte-derived macrophages. Glyc101-induced TNFα production was observed to be mediated via the TLR-2 and dectin-1 receptors, receptor tyrosine kinases and NFκB activation. In murine wound macrophages, Glyc101 potentiated phorbol 12-myristate 13-acetate-induced respiratory burst. In vivo, implantation of Glyc101-enriched polyvinyl alcohol-sponges at the wound-site induced TNFα expression in macrophages. Consistently, Glyc101 induced TNFα expression in wound-site macrophages isolated from two patients with chronic wounds. These observations establish the translational significance of the net findings of this study. Activation of wound macrophages by Glyc101 represents one of the potential mechanisms by which this β-glucan may benefit chronic wounds where inefficient inflammatory response is one of the underlying causes of impaired healing.

• Authors: Sashwati Roy, Ryan Dickerson, Savita Khanna, Eric Collard, Urmila Gnyawali, Gayle M Gordillo, Chandan K Sen
• Journal: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society (Wound Repair Regen) 2011 May-Jun Vol. 19 Issue 3 Pg. 411-9 ISSN: 1524-475X [Electronic] United States
• PMID: 21518092 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2011 by the Wound Healing Society.

Chemical References

• Lectins, C-Type
• Membrane Proteins
• NF-kappa B
• Nerve Tissue Proteins
• Tumor Necrosis Factor-alpha
• beta-Glucans
• dectin 1
• Interleukin-10

Topics

• Animals
• Cell Wall (chemistry)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Humans
• Interleukin-10 (metabolism)
• Lectins, C-Type
• Macrophage Activation (immunology)
• Macrophages (drug effects, immunology, metabolism)
• Membrane Proteins (metabolism, pharmacology)
• Mice
• Mice, Inbred C57BL
• NF-kappa B (physiology)
• Nerve Tissue Proteins (metabolism, pharmacology)
• Oxidation-Reduction
• Phagocytosis (drug effects, immunology, physiology)
• Saccharomyces cerevisiae (immunology, metabolism)
• Signal Transduction (drug effects, immunology)
• Tumor Necrosis Factor-alpha (metabolism)
• Wound Healing (drug effects)
• beta-Glucans (pharmacology)