gms | German Medical Science

Introduction: D-Dopachrome Tautomerase (D-DT/MIF-2) is a member of the macrophage migration inhibitory factor (MIF) cytokine superfamily, and a close structural homologue of MIF. MIF and D-DT have been reported to be involved in obesity, but there is little known about the regulation of D-DT in adipose tissue inflammation and wound healing. This study aimed to examine the role of D-DT in macrophage recruitment, in inflamed adipose tissue, and in wound repair.

Methods: Subcutaneous adipose tissue was collected from 54 healthy donors and 28 donors with acutely inflamed wounds undergoing wound debridement. The expression of D-DT was measured by RT-PCR and ELISA, and cell-specific D-DT expression was visualized by immunohistochemistry. Additionally, the role of D-DT in the proliferation, viability, and repair response of human dermal fibroblasts was investigated in vitro. Finally, we evaluated the expression of adipose tissue-derived D-DT and receptor expression as well as macrophage migration in an in vivo model of adipose inflammation comprising LPS injection into epididymal fat pads of mice.

Results: D-DT protein levels and mRNA expression were significantly decreased in subcutaneous adipose tissue adjacent to acutely inflamed wounds. In healthy subjects, D-DT was expressed in adipocytes, while in inflamed subcutaneous adipose tissue D-DT was primarily localized in infiltrating inflammatory cells. D-DT improved fibroblast viability, increased proliferation, and showed a beneficial effect on wound healing. Interestingly, expression of the MIF and D-DT receptor CD74 was down-regulated while the MIF receptors CXCR2 and CXCR4 were upregulated indicating that the MIF-CXCR2/4 axis may promote recruitment of inflammatory cells into adipose tissue.

Conclusion: Our results describe a reciprocal role of D-DT to MIF in inflamed adipose tissue, and indicate that D-DT may be beneficial in wound repair by improving fibroblast survival and proliferation.