Abstract: Objective: To explore the effects of Substance P (SP) and FK-506 on the production of cathelicidin CAMP and the activation of NF-κB in human keratinocytes. Methods: The HaCaT cells were cultured in vitro and treated with SP and/or FK-506 for 24 h. The expression levels of CAMP mRNA and protein were detected by qRT-PCR and western blotting respectively. The nuclear translocation of NF-κB/p65 was visualized by using an immunofluorescence staining. Results: The upregulations of CAMP mRNA and protein were detected in the cells treated with SP, of which the cells treated with 1μM SP for 24h showed the maximum stimulation effect, with a significant difference compared with untreated group (P<0.05). The nuclear translocation of NF-κB/p65 protein was also observed in HaCaT cells treated with SP for 30 min, with a significant difference compared with untreated cells (P<0.05). Thereafter, the nuclear translocation of NF-κB/p65 was diminished with time. FK-506 exerted a potent suppression in the nuclear translocation of NF-κB/p65 and in the expression of CAMP.  There was a statistically significant difference between the group treated with SP alone and the group treated in combination of SP and FK-506 (P<0.05). Conclusion: SP induces the production of cathelicdin in cultured keratinocytes through the activation of NF-κB signaling pathway. The regimens aiming at suppression of “SP-NF-κB activation-cathelicidin” might be a potential new target for the treatment of rosacea.

Key words: Substance P')">

Substance P, keratinocytes, cathelicidin, NF-κB, rosacea