Vesicular LL-37 contributes to inflammation of the lesional skin of palmoplantar pustulosis.
Murakami. Masamoto M; Kaneko. Takaaki T; Nakatsuji. Teruaki T; Kameda. Kenji K; Okazaki. Hidenori H; Dai. Xiuju X; Hanakawa. Yasushi Y; Tohyama. Mikiko M; Ishida-Yamamoto. Akemi A; Sayama. Koji K
Key Findings
- PPP vesicle fluid has ~30‑fold higher LL‑37 levels than normal sweat (2.87 µM vs 0.09 µM).
- Removing LL‑37 from the fluid significantly lowers IL‑8 mRNA induction in skin models, while other cytokines are less affected.
- Adding LL‑37 back restores IL‑17C, IL‑8, IL‑1α, and IL‑1β expression; proteinase 3 in the fluid converts the precursor to active LL‑37.
- Early vesicles are filled with CD68‑positive mononuclear cells and the surrounding epidermis releases chemokine CCL2.
Practical Outcomes
- For self‑experimenters, boosting LL‑37 (e.g., with topical cathelicidin products) may worsen inflammatory skin conditions like PPP, so caution is advised. There’s no dosage recommendation, but avoiding excess LL‑37 exposure on inflamed skin could help reduce flare‑ups.
Summary
The study found that fluid from early skin blisters in palmoplantar pustulosis contains a lot of the antimicrobial peptide LL‑37, which can trigger inflammatory signals (especially IL‑8) in skin cells and likely makes the rash worse. The fluid also has the enzyme that activates LL‑37, so the peptide can act locally to drive inflammation.
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.
Study Information
pubmed
2014
2014-10-16T00:00:00.000Z
10.1371/journal.pone.0110677
39
44