Substance P receptor expression in human skin keratinocytes and fibroblasts

There is increasing evidence that neuropeptides, especially substance P (SP), may be involved in the pathogenesis of cutaneous allergic inflammation (CAI).

To investigate expression of the SP receptor (neurokinin-1 receptor, NK-1R) in human epidermal keratinocytes and dermal fibroblasts and its potential influence in CAI.

HaCaT cells (a human epidermal keratinocyte cell line) and dermal fibroblasts were cultured. The expression of NK-1R protein was examined by immunohistochemistry, and the mRNA level was detected by semiquantitative reverse transcriptase-polymerase chain reaction. The modulation of NK-1R expression in HaCaT cells and fibroblasts was detected by flow cytometry and Western blotting analysis.

NK-1R expression was found in HaCaT cells and fibroblasts. The expression of NK-1R mRNA in fibroblasts was weaker than in HaCaT cells. SP and interferon (IFN)-gamma significantly upregulated the expression of NK-1R. [d-Arg(1), d-Trp(7,9) Leu(11)]-SP (Spantide I), a panspecific NK-1R antagonist, reduced the expression of NK-1R stimulated by SP.

HaCaT cells and fibroblasts can express NK-1R at protein and transcription levels, and the expression was modulated by SP, IFN-gamma and Spantide I. This indicates that keratinocytes and fibroblasts are involved in the regulation of skin immunity and that NK-1R may play an important role in the pathogenesis of CAI.