title: Cathelicidin antimicrobial peptide LL-37 in cholesteatoma enables keratinocyte reactivity with cytosolic DNA.
abstract: The purpose of this study was to determine whether self-DNA can trigger the inflammatory response in cholesteatoma. Specimens were collected from nine patients with invasive cholesteatoma, nine patients with attic-type cholesteatoma (pars flaccida was perforated in five patients and intact in four) and four healthy skins. Expression and localization of LL-37 and interferon-alpha were detected by immunofluorescence and immunoblot analysis. Cultures of human cholesteatomatous keratinocytes were exposed to CpG DNA, LL-37 or CpG DNA complexed to LL-37 for 24 h. Expression of interferon-alpha was detected by RT-PCR. We detected abundant cytosolic DNA, increased LL-37 and interferon-alpha in keratinocytes in invasive cholesteatoma and attic-type cholesteatoma with pars flaccida perforation, but not in attic-type cholesteatoma with pars flaccida intact and normal skin. In cultured keratinocytes, LL-37-DNA complexes induced IFN-α expression. These data suggest that cytosolic DNA is an important disease-associated molecular pattern that triggers the inflammation response in cholesteatoma. Furthermore, LL-37 played an important role in DNA-triggered inflammation. Thus, we have identified a link between cytosolic DNA, LL-37 and autoinflammation in cholesteatoma, providing new potential targets for the treatment of this disease.
authors.affiliation: Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chi
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: S
authors.initials: S
authors.lastname: Qin
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology; D054804:Cathelicidins / Q000378:metabolism*; D002478:Cells, Cultured; D002781:Cholesteatoma / Q000235:genetics* / Q000276:immunology*; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000276:immunology / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D012333:RNA, Messenger; D004247:DNA