Pathologic role of excessive DNA as a trigger of keratinocyte proliferation in psoriasis.

In this study, we explored excessive DNA as a potential trigger of psoriasis using cultured human keratinocytes and psoriatic skin tissues. We demonstrated that human genomic DNA fragments induced tumor necrosis factor-α (TNF-α) expression, hyperproliferation, and overexpression of heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor α (TGF-α), accompanied by defective expression of keratins 1 and 10 in cultured normal human epidermal keratinocytes, which have a similar phenotype as that of keratinocytes in psoriatic skin lesions. In psoriatic lesions, we found high levels of double-stranded (ds)DNA fragments, accompanying keratinocytes expressing Ki-67, HB-EGF and TNF-α. In addition, we showed that 1,25-dihydroxyvitamin D3 inhibited genomic DNA fragment-induced TNFA and interleukin-1β (IFNB) expression in human keratinocytes, and intact function of cathelicidin antimicrobial peptide was required for this effect. These results suggest that excessive dsDNA fragments likely act as a risk factor for immune activation in psoriasis, and the active form of vitamin D can prevent genomic DNA-mediated skin inflammation via cathelicidin antimicrobial peptide. PMID: 32415989 [PubMed - as supplied by publisher]
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research