Abstract
“Pustulosis palmaris et plantaris”, or palmoplantar pustulosis (PPP), is a chronic pustular dermatitis characterized by intraepidermal palmoplantar pustules. Although early stage vesicles (preceding the pustular phase) formed in the acrosyringium contain the antimicrobial peptides cathelicidin (hCAP-18/LL-37) and dermcidin, the details of hCAP-18/LL-37 expression in such vesicles remain unclear. The principal aim of the present study was to clarify the manner of hCAP-18/LL-37 expression in PPP vesicles and to determine whether this material contributed to subsequent inflammation of lesional skin. PPP vesicle fluid (PPP-VF) induced the expression of mRNAs encoding IL-17C, IL-8, IL-1α, and IL-1β in living skin equivalents, but the level of only IL-8 mRNA decreased significantly upon stimulation of PPP vesicle with depletion of endogenous hCAP-18/LL-37 by affinity chromatography (dep-PPP-VF). Semi-quantitative dot-blot analysis revealed higher concentrations of hCAP-18/LL-37 in PPP-VF compared to healthy sweat (2.87±0.93 µM vs. 0.09±0.09 µM). This concentration of hCAP-18/LL-37 in PPP-VF could upregulate expression of IL-17C, IL-8, IL-1α, and IL-1β at both the mRNA and protein levels. Recombinant hCAP-18 was incubated with dep-PPP-VF. Proteinase 3, which converts hCAP-18 to the active form (LL-37), was present in PPP-VF. Histopathological and immunohistochemical examination revealed that early stage vesicles contained many mononuclear cells but no polymorphonuclear cells, and the mononuclear cells were CD68-positive. The epidermis surrounding the vesicle expresses monocyte chemotactic chemokine, CCL2. In conclusion, PPP-VF contains the proteinase required for LL-37 processing and also may directly upregulate IL-8 in lesional keratinocytes, in turn contributing to the subsequent inflammation of PPP lesional skin.
Highlights
palmoplantar pustulosis (PPP)-VF contains a higher concentration of hCAP-18/LL37 than it in eccrine sweat
We reported that IL-17 (A, C, and F), IL-22, and IL8 mRNAs were upregulated in the lesional skin of PPP patients [32]; confirmed that PPP vesicle fluid (PPP-VF) could upregulate the expression of IL-17C, IL-8, IL-1a, and IL-1b in living skin equivalents (LSEs) keratinocytes; and that endogenous hCAP-18/LL-37 induced high-level IL-8 synthesis (Fig. 1)
GST-rhCAP-18 was incubated with depleted PPP-VF, and the presence of processed LL-37 confirmed thereafter (Fig. 4A)
Summary
The principal aim of the present study was to clarify the manner of hCAP-18/LL37 expression in PPP vesicles and to determine whether this material contributed to subsequent inflammation of lesional skin
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