SUBSTANCE-P AND KERATINOCYTE ACTIVATION MARKERS - AN IN-VITRO APPROACH

Substance P (SP) released by cutaneous C fibres is involved in the phy siopathology of cutaneous lesions, As normal human keratinocytes have been reported to express SP receptors, we studied the effects of SP on keratinocyte activation markers such as ICAM-1 induction and cytokine production. Human keratinocytes derived from skin obtained during pla stic surgery were cultured in defined medium (MCDB 153) and were stimu lated by SP, Flow cytometry analysis showed that SP (10(-7) and 10(-5) M) as well as the specific NK1 agonist Sar(9)Met(O-2)(SP)-S-11 (Sar M et) induced a slight but significant expression of ICAM-1 at the cell surface during treatment periods of 24 h and 48 h, SP (10(-5) M) also induced a significant but transient increase in the production of IL-1 alpha, IL-1 beta, IL-1 receptor antagonist and IL-8 which was detecta ble by ELISA techniques 6 h after stimulation. This elevation returned to constitutive levels 24 or 48 h postinduction, TNF alpha secretion was detected in stimulated cells only after 48 h, These results sugges t that SP can activate keratinocytes and support its role in the local inflammatory reaction.