IL-25 improves diabetic wound healing through stimulating M2 macrophage polarization and fibroblast activation.

Abstract

BACKGROUND:

Persistent chronic inflammation is one of the main pathogenic characteristics of diabetic wounds. The resolution of inflammation is important for wound healing and extracellular matrix (ECM) formation. Interleukin (IL)-25 can modulate the function of macrophage and fibroblast, but its role and mechanism of action in the treatment of diabetic wounds remain largely unclear.

METHODS:

The mice were categorized into diabetic, diabetic + IL-25 and control groups. Human monocytic THP-1 cell line and human dermal fibroblast (HDF) were stimulated under different IL-25 conditions. Then, flow cytometry, real-time quantitative PCR (RT-qPCR), Western blot (WB), and immunofluorescence (IF) assays were carried out.

RESULTS:

The mice in diabetes group (DG) had a slower wound healing rate, more severe inflammation, less blood vessels and more disordered collagen than those in control group (CG). Intradermal injection of IL-25 could improve these conditions. IL-25 promoted M2 macrophage polarization and fibroblast activation in DG and high-glucose environment. The phenomenon, which was dependent on PI3K/AKT/mTOR and TGF-β/SMAD signaling, could be blocked by LY294002 and LY2109761.

CONCLUSION:

IL-25 may serve as a therapeutic target to improve wound healing in diabetic mice.

• Authors: Shiyan Li, Xiaofeng Ding, Hao Zhang, Youjun Ding, Qian Tan
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 106 Pg. 108605 (May 2022) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 35149293 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier B.V.

Chemical References

• Interleukins

Topics

• Animals
• Diabetes Mellitus, Experimental (metabolism)
• Fibroblasts (metabolism)
• Humans
• Interleukins (pharmacology)
• Macrophage Activation
• Macrophages (metabolism)
• Mice
• Phosphatidylinositol 3-Kinases (metabolism)
• THP-1 Cells
• Wound Healing