Amarogentin Displays Immunomodulatory Effects in Human Mast Cells and Keratinocytes

Figure 6

Simplified working hypothesis for the reaction mechanism of TAS2R agonists on cellular interactions among mast cells, T cells, and keratinocytes in the epidermis and uppermost dermis of inflamed skin. The reaction might be triggered by substance P (SP) released from nerve cells. The TAS2R agonist amarogentin inhibits the secretion of TNF-α from mast cells. Furthermore, the section of MMP-1 and IL-8 is directly inhibited by amarogentin in histamine and TNF-α costimulated human keratinocytes. Reduced MMP-1 expression results in reduced degradation of the basement membrane and reduced T cell transmigration to the epidermis. This may reduce the secretion of inflammatory cytokines by T cells in the epidermis.