Therapeutic Effect of GGsTop, Selective Gamma-glutamyl Transpeptidase Inhibitor, on a Mouse Model of 5-Fluorouracil-induced Oral Mucositis.

BACKGROUND/AIM: Regulatory T cells (Tregs) play a crucial role in inflammatory responses by regulating the activity of various immune cells. M2 macrophages induced by IL-10 and TGF-β exhibit anti-inflammatory functions and induce Treg differentiation. Although the beneficial effects of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) on various diseases have been widely reported, the mechanisms, through which it alleviates allergic contact dermatitis (ACD) via Tregs and macrophages, are not well understood. Therefore, this study aimed to explore whether BDB suppresses ACD and induces Treg generation.

MATERIALS AND

METHODS

Mice were sensitized with 1% dinitrochlorobenzene (DNCB), followed by the application of 0.3% DNCB to their ears every 3 days for 31 days. BDB (100 mg/kg) was administered orally once daily throughout the 31 days. Cytokine and transcription factor expression were analyzed via real-time PCR and western blotting, while CD4+Foxp3+ T cell differentiation and T cell proliferation were evaluated using flow cytometry.

RESULTS

BDB exhibited therapeutic efficacy in mice with ACD. In this study, the administration of BDB promoted the upregulation of transforming growth factor beta (TGF-β)-dependent CD4+Foxp3+ T cells. BDB elicited T cell hypo-responsiveness and suppressed the expression of cytokines related to the Th1, Th2, and Th17 cell subsets. BDB-M2 macrophages directly mediated the differentiation of CD4+Foxp3+ T cells from CD4+ T cells and concurrently suppressed the proliferation of CD4+ T cells.

CONCLUSION

BDB augments M2 macrophage function and induction of Tregs confers effective protection against ACD in mice. Consequently, BDB may represent a promising therapeutic approach for the treatment of inflammatory skin diseases.