Interleukin-37 promotes wound healing in diabetic mice by inhibiting the MAPK/NLRP3 pathway

Diabetic foot ulcer (DFU) is a common complication of diabetes characterized by increased inflammation and a slowed healing process for wounds. Interleukin-37 (IL-37) may act as an alarm to alert the immune system when released by epithelial barrier tissues during trauma or infection, exerting a broad range of protective effects in several diseases. The objective of this study was to examine the regenerative capabilities of IL-37 in improving the healing of diabetic wounds. Using streptozotocin (STZ)-induced diabetic mice, we found that diabetic IL-37Tg mice showed a significantly accelerated healing process. In addition, IL-37 strongly suppressed MAPK signaling pathway by inhibiting phosphorylation of the P38 and ERK. Moreover, IL-37 reduced the expression of Nod-like receptor protein-3 (NLRP3) and mature IL-1β. These results thus indicated that IL-37 inhibition of IL-1β production is mediated by suppressing the initial priming step and by inhibiting the NLRP3 inflammasome activation. Taken together, our findings demonstrated the promising regulatory activity of IL-37 against IL-1β production and indicated that IL-37 has the potential to be effective as a novel therapeutic agent for treatment of wound. Our data indicate a beneficial effect of IL-37 in diabetic wounds, suggesting a therapeutic potential for this cytokine in diabetic ulcer management.