Expression of antimicrobial peptides in psoriasis mouse models

Abstract

Psoriasis is a chronic, inflammatory autoimmune skin disease. Histologically, the hallmark of psoriasis is the presence of a greatly thickened nucleated keratinocyte layer with uniform elongation of the rete ridges caused by hyperproliferation of keratinocytes and dermal infiltration by activated T cells, neutrophils and dendritic cells. Psoriasis has traditionally been classified as a Th1 and Th17-mediated disease. Despite the current focus on T cells in the pathogenesis of psoriasis, the keratinocytes within the epidermis of psoriatic plaques are clearly abnormal in many respects. The excessive production of antimicrobial peptides (AMPs) is one of the abnormal functions of psoriatic keratinocytes. AMPs are small, evolutionarily conserved proteins that can be found mostly in the epithelium. They are effector molecules of innate immunity, with high antimicrobial activity against many bacteria, fungi and some viruses. AMPs of the skin include human β-defensin (hBD) 1-3, cathelicidin hCAP18/LL-37, ribonucleases (RNases) such as RNase 7, and S-100-proteins such as psoriasin (S100A7) and others. Cathelicidin, β-defensins, S100 proteins, RNase 7, lysozyme, elafin and neutrophil gelatinase associated liocalin are highly expressed in psoriatic lesions.Recently, various studies using imiquimod (IMQ) and IL-23-induced mouse model have been reported to explore immunological significance of psoriasis. However, AMPs expression in the IMQ-and IL-23-induced psoriasis models remains unclear.In this study, we evaluated the protein and mRNA expression of the AMPs such as cathelicidin related antimicrobial peptides (CAMP), mouse β-defensin 3 (mBD3), psoriasin (S100A7) in IMQ-and IL-23-induced psoriasis mouse models and compared the expression level of the AMPs between two mouse models. In addition, we investigated whether ustekinumab which blocks IL-12 and IL-23, could reduce AMP expression levels in these mouse models.We found that protein and mRNA expression levels of CRAMP, mBD3, and S100A7 were markedly increased in both psoriasis mouse models. There were no significant differences in AMP expression levels between IMQ- and IL-23-induced mouse models. Ustekinumab treatment led to reversion of AMP expression level to normal. These data showed that AMP expression of both psoriasis mouse models correlate well with the characteristic of human psoriasis, therefore AMP expression levels could be used as an indicator of treatment efficacy.