Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands.

Abstract

Here we show that keratinocytes in psoriatic lesional skin express increased Toll-like receptor (TLR) 9 that similarly localizes with elevated expression of the cathelicidin antimicrobial peptide LL-37. In culture, normal human keratinocytes exposed to LL-37 increased TLR9 expression. Furthermore, when keratinocytes were exposed to LL-37 and subsequently treated with TLR9 ligands, such as CpG or genomic DNA, they greatly increased production of type I IFNs. This response mimicked observations in the epidermis of psoriatic lesional skin as keratinocytes in psoriatic lesions produce greater amounts of IFN-β than normal skin lacking LL-37. The mechanism for induction of type I IFNs in keratinocytes was dependent on TLR9 expression but not on a DNA-LL-37 complex. These findings suggest that keratinocytes recognize and respond to DNA and can actively participate in contributing to the immunological environment that characterizes psoriasis.

• Authors: Shin Morizane, Kenshi Yamasaki, Beda Mühleisen, Paul F Kotol, Masamoto Murakami, Yumi Aoyama, Keiji Iwatsuki, Tissa Hata, Richard L Gallo
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 132 Issue 1 Pg. 135-43 (Jan 2012) ISSN: 1523-1747 [Electronic] United States
• PMID: 21850017 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antimicrobial Cationic Peptides
• Cathelicidins
• Interferon Type I
• Ligands
• TLR9 protein, human
• Toll-Like Receptor 9
• Interferon-beta
• DNA

Topics

• Antimicrobial Cationic Peptides
• Biopsy
• Cathelicidins (genetics, immunology, metabolism)
• Cells, Cultured
• CpG Islands (genetics, immunology)
• DNA (immunology, pharmacology)
• Epidermal Cells
• Gene Expression (immunology)
• Humans
• Interferon Type I (genetics, immunology, metabolism)
• Interferon-beta (genetics, immunology, metabolism)
• Keratinocytes (cytology, physiology)
• Ligands
• Psoriasis (immunology, physiopathology)
• Toll-Like Receptor 9 (immunology, metabolism)