건선 피부에서 Toll-like receptors와 antimicrobial peptides의 발현과 혈청 내 비타민 D과의 관계

Abstract

Background: Psoriasis is a chronic relapsing immune-mediated skin disease characterized by rapid turnover of the epidermal keratinocytes. Vitamin D, Toll-like receptors (TLRs), and antimicrobial peptides (AMPs) such as human beta defensins (HBDs) and cathelicidins (LL-37) can modulate the immune system through a variety of ways in psoriasis.

Purpose: The objective of the present study was to determine, whether epidermal keratinocytes of psoriatic skin show overexpression or different distribution pattern of TLRs, AMPs, and vitamin D receptor (VDR) compared with atopic dermatitis and healthy control and whether an association exists between the serum 25(OH)D concentration and the TLRs, AMPs, and VDR expression of skin sample of psoriasis.

Materials and Methods: From January 2008 to June 2008, a total of 12 newly diagnosed psoriasis patients were enrolled in this study. The specimens from lesional (PP) and perilesional skin (PN) of psoriasis patients and of 12 age- and sex-matched atopic dermatitis (AD) patients and of 12 healthy normal controls (NN) were studied using immunohistochemical staining. Serum vitamin D levels were determined by radioimmunoassay.

Results: Compared to atopic dermatitis and normal controls, the distribution of TLR1, TLR2, TLR4, HBD2 and LL-37 in psoriasis lesion occurs more strongly in the upper epidermis. PP skin showed more expression of TLR1 and less expression of TLR2, HBD3 and VDR than NN skin. PP skin also showed more expression of TLR1 and less expression of TLR2, HBD3 and VDR than AD skin. In PP skin, TLR 1, TLR4, HBD2 and LL-37 expression were increased but TLR2, HBD3 and VDR expression was decreased than PN skin. The expression of TLR2 and TLR1, PASI score and TLR4 expression in PP skin showed a positive correlation. TLR2 and VDR in PN skin skin also showed a positive correlation. But, the expression of TLR2 negatively correlated with the expression of VDR in PP skin. HBD2 and LL-37 in psoriasis tissue showed lower expressions with a trend towards lower serum 25(OH)D levels.

Conclusion: The epidermal keratinocytes of PP skin shows different amount and distribution pattern of TLRs, AMPs and VDR compared with PN, AD and NN skin. The correlation of vitamin D to the AMP expression in keratinocytes also showed in psoriasis patient. These results support the concept that correlations among TLRs, AMPs and vitamin D in psoriasis may play a role in development of psoriasis lesion. Based on the present results, therapies targeting control of TLRs, AMPs and vitamin D might provide new approaches in the management of psoriasis and other inflammatory skin diseases.