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

• Published in: International immunopharmacology Vol. 106; p. 108605
• Main Authors: Li, Shiyan, Ding, Xiaofeng, Zhang, Hao, Ding, Youjun, Tan, Qian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2022; Elsevier BV
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Blood vessels; Cell activation; Collagen; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; Extracellular matrix; Fibroblast; Fibroblasts; Fibroblasts - metabolism; Flow cytometry; Humans; Immunofluorescence; Inflammation; Interleukin-25; Interleukins; Interleukins - pharmacology; Macrophage; Macrophage Activation; Macrophages; Macrophages - metabolism; Mice; Monocytes; Phosphatidylinositol 3-Kinases - metabolism; Polarization; Smad protein; Therapeutic targets; THP-1 Cells; TOR protein; Wound Healing; PBS; Wound healing; IL; DG; CG; VEGF; MT; HDF; WB; ECM; α-SMA; BSA; Interleukin-25; TGF-β1; Diabetes; Fibroblast; RT-qPCR; IF; HE; Macrophage
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2022.108605

•IL-25 promoted M2 macrophage polarization and fibroblast activation in skin wound of diabetic mice and high-glucose environment.•IL-25 alleviated diabetic wound inflammation and impaired extracellular matrix accumulation.•IL-25 may improve wound healing in diabetic mice through PI3K/AKT/mTOR and TGF-β/SMAD signaling pathways. 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. 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. 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. IL-25 may serve as a therapeutic target to improve wound healing in diabetic mice.