TLN-58, an Additional hCAP18 Processing Form, Found in the Lesion Vesicle of Palmoplantar Pustulosis in the Skin

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• 作者：Masamoto Murakami¹ ; ^{mamuraka@m.ehime-u.ac.jp} ; Kenji Kameda² ; Hiroki Tsumoto³ ; Teruko Tsuda¹ ; Kana Masuda¹ ; Ryo Utsunomiya¹ ; Hideki Mori¹ ; Yuri Miura³ ; Koji Sayama¹
• 关键词：dep-PPP-VF ; endogenous hCAP-18/LL-37 depleted PPP vesicle fluid ; ELA2 ; elastase-2 ; GST ; glutathione S-transferase ; hCAP ; human cathelicidin ; His ; histidine ; LC-MALDI-TOF/TOF ; liquid chromatography&ndash ; matrix-assisted laser desorption/ionization time-of-flight/time-of-flight ; MRSA ; methicillin-resistant Staphylococcus aureus ; NHK ; normal human keratinocyte ; PPP ; palmoplantar pustulosis ; PPP-VF ; PPP vesicle fluid ; rhCAP ; recombinant human cathelicidin ; SA ; Staphylococcus aureus
• 刊名：Journal of Investigative Dermatology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：137
• 期：2
• 页码：322-331
• 全文大小：1259 K
• 卷排序：137

文摘

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.