Differential regulation of thymus- and activation-regulated chemokine induced by IL-4, IL-13, TNF-alpha and IFN-gamma in human keratinocyte and fibroblast.

ABSTRACT

The CC chemokine thymus- and activation-regulated chemokine (TARC/CCL17) acts on CC chemokine receptor 4 (CCR4), which is known to be selectively expressed in Th2 cells. In order to compare the regulatory profiles of TARC production by tumor necrosis factor-alpha (TNF-alpha), IFN-gamma, interleukin-4 (IL-4) and IL-13 in keratinocytes and fibroblasts, HaCaT cells, a human keratinocyte cell line, and NG1RGB cells, a human skin fibroblast cell line, were used. The expression of TARC protein was measured using enzyme-linked immunosorbent assay (ELISA), and the mRNA level was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The spontaneous expression of TARC protein and mRNA levels were augmented by TNF-alpha and IFN-gamma and were inhibited by IL-4 and IL-13 in the keratinocytes. The fibroblasts expressed the TARC protein and mRNA only in the presence of IL-4+TNF-alpha or IL-13+TNF-alpha stimulation. IFN-gamma further enhanced the IL-4+TNF-alpha or IL-13+TNF-alpha-induced TARC production in the fibroblasts. Thus, TNF-alpha and IFN-gamma -induced TARC production was differentially regulated by IL-4 and IL-13 in human keratinocytes and fibroblasts.