Diabetic Wounds Exhibit Decreased Ym1 and Arginase Expression with Increased Expression of IL-17 and IL-20

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Abstract
Objective: Impaired wound healing in diabetic (DB) patients is a significant health problem; however, the roles that cytokines and innate immune cells contribute to this impaired healing are not completely understood. Approach: A mouse model was used to compare the innate immune response during DB and normal wound healing. Two 5-mm full-thickness wounds were created on the dorsal skin of BKS.Cg-m+/+Leprdb/J (DB) and C57BL/6 (wild-type) mice. Innate immune cell markers and cytokine mRNA levels were measured in wound biopsies during the first week of healing. Results: Innate immune cell influx (typified by the Gr-1 neutrophil marker and the Ym1 macrophage marker) was delayed in the DB wounds. Expression of the M2 macrophage-related genes, Ym1 and arginase 1, was significantly reduced in the DB wounds. PCR array analysis demonstrated altered cytokine expression in DB wounds. Most prominently, both interleukin (IL)-17 and IL-20 mRNA levels were significantly increased in the DB wounds. Innovation: This is the first study to identify increased levels of IL-17 and IL-20 in DB wounds. These cytokines are also elevated in the inflammatory skin disorder, psoriasis; thus, they may be potential therapeutic targets to aid in DB wound healing. Conclusion: The entire cytokine profile of DB wounds over the course of healing is not completely understood. This study suggests that the IL-17 and IL-20 families of cytokines should be further analyzed in the context of DB wound healing.

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