title: TLN-58, an Additional hCAP18 Processing Form, Found in the Lesion Vesicle of Palmoplantar Pustulosis in the Skin.
abstract: We previously reported that the early vesicle of the palmoplantar pustulosis (PPP) vesicle originated from eccrine sweat in the acrosyringium and that the PPP vesicle contains the antimicrobial peptide human cathelicidin-18/LL-37. The concentration of LL-37 was sufficient to induce the subsequent inflammation in lesions and human keratinocytes, and the PPP vesicles contained additional small fragments of human cathelicidin-18, of approximately 7 kDa, which have not been identified. The aim of the present study was to clarify the additional processed forms found in PPP vesicles and their physiological effects on normal keratinocytes and sweat gland cells. Lesional PPP vesicles were collected from PPP patients, and endogenous human cathelicidin-18/LL-37 was depleted using a LL-37 antibody affinity column. A designed recombinant human cathelicidin-18 peptide was prepared and incubated with the depleted PPP vesicle fluid to confirm the additional processed form. In-gel digestion analysis and protein sequencing confirmed the additional form as TLN-58. TLN-58 up-regulated IL-17C, IL-8, IL-23, IL-1α, and IL-1β mRNA and protein expression in normal human keratinocytes and also showed antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, and group A Streptococcus species, similar to LL-37. This additional form could be involved in the continued inflammation in PPP lesions.
authors: Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan. Electronic address: mamuraka@m.ehime-u.ac.jp.
authors: Masamoto
authors: M
authors: Murakami
authors: Advanced Research Support Center, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Kenji
authors: K
authors: Kameda
authors: Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors: Hiroki
authors: H
authors: Tsumoto
authors: Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Teruko
authors: T
authors: Tsuda
authors: Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Kana
authors: K
authors: Masuda
authors: Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Ryo
authors: R
authors: Utsunomiya
authors: Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Hideki
authors: H
authors: Mori
authors: Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors: Yuri
authors: Y
authors: Miura
authors: Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Koji
authors: K
authors: Sayama
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000032:analysis* / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics; D006801:Humans; D011565:Psoriasis / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000737:chemistry; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D012333:RNA, Messenger; D054804:Cathelicidins