Il-22-Fc in cutaneous wound healing response

Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. When compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU. There are 45 samples in total (nine groups n=5/group). We have prepared the RNA from Diabetic Foot Ulcer Skin wounds. The following is the experimental design: Groups 1-4: 24 hrs time point; Groups 5-9: day7 post wound; Group 1: db/db females, n=5, anti Ragweed; Group 2: db/db females, n=5 IL-22 Fc; Group 3: db/db females, n=5 VEGF; Group 4: db/db females, n=5 PDGF; Group 5: dbm females n=5, PBS (lean control mice); Group 6: db/db females, n=5, anti-Ragweed; Group 7: db/db females, n=5 IL-22 Fc; Group 8: db/db females, n=5 VEGF; Group 9: db/db females, n=5 PDGF anti-Ragweed (50 ug) and Il-22 Fc (20 ug). For groups 1-4, wound (6mm) will be created on Day0 and receive one dose of topical treatment. Mice will be euthanized 24 hrs post topical treatment and wound tissue will be harvested. For groups 5 through 9 wound will be created on day 0 and dosed topically on Day0, Day2, day4, day 6. Mice will be euthanized on Day 7 and wound tissue harvested and RNA prepared.