Sphingosylphosphorylcholine stimulates cellular fibronectin expression through upregulation of IL-6 in cultured human dermal fibroblasts

Sphingosylphosphorylcholine (SPC) has been reported to stimulate wound healing by its potent mitogenic effect. Fibronectin (FN) is a cell-adhesion protein that plays an important role in cell migration and collagen deposition during wound healing. In order to elucidate further the mechanism involved in the accelerated wound healing stimulated by SPC, we studied the role of SPC in FN production in cultured human dermal fibroblasts. We demonstrated that SPC dose- and time-dependently enhanced the expression of FN in human dermal fibroblast at the protein and mRNA levels. IL-6 is known to stimulate the production of FN in fibroblasts. SPC also markedly induced IL-6 production in cultured human dermal fibroblasts in a dose- and time-dependent manner. We also demonstrated that FN mRNA expression in human dermal fibroblasts was upregulated 4 h after IL-6 treatment. Moreover, pretreatment with neutralizing anti-IL-6 antibodies partially blocked the upregulation of FN mRNA expression induced by SPC in human dermal fibroblasts. These results indicate that SPC may stimulate FN synthesis through IL-6 production in cultured human dermal fibroblasts.