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Vesicular LL-37 contributes to inflammation of the lesional skin of palmoplantar pustulosis.

Murakami M, Kaneko T, Nakatsuji T, Kameda K, Okazaki H, Dai X, Hanakawa Y, Tohyama M, Ishida-Yamamoto A, Sayama K - PLoS ONE (2014)

Bottom Line: 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).Proteinase 3, which converts hCAP-18 to the active form (LL-37), was present in PPP-VF.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.

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.

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MCP-1 expression in PPP lesion skin and healthy skin.In lesion skin, strong expression of MCP-1 was detected around the PPP vesicle in the epidermis (Figs. 6a, b). In addition, acrosyringium in the lesions skin also showed the protein expression (Fig. 6c), but not in healthy skin (Fig. 6e, f). The eccrine pore at the surface of skin showed weak positive staining locating (Fig. 6f, arrowhead). (Original magnifications: a, c, d, e: 40×, b, f: 100×).
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pone-0110677-g006: MCP-1 expression in PPP lesion skin and healthy skin.In lesion skin, strong expression of MCP-1 was detected around the PPP vesicle in the epidermis (Figs. 6a, b). In addition, acrosyringium in the lesions skin also showed the protein expression (Fig. 6c), but not in healthy skin (Fig. 6e, f). The eccrine pore at the surface of skin showed weak positive staining locating (Fig. 6f, arrowhead). (Original magnifications: a, c, d, e: 40×, b, f: 100×).

Mentions: The epidermis surrounding the PPP vesicle expressed the MCP-1 protein (Fig. 6a–c, e, f). No signal was detected from pre-immune mouse IgG (Fig. 6d).


Vesicular LL-37 contributes to inflammation of the lesional skin of palmoplantar pustulosis.

Murakami M, Kaneko T, Nakatsuji T, Kameda K, Okazaki H, Dai X, Hanakawa Y, Tohyama M, Ishida-Yamamoto A, Sayama K - PLoS ONE (2014)

MCP-1 expression in PPP lesion skin and healthy skin.In lesion skin, strong expression of MCP-1 was detected around the PPP vesicle in the epidermis (Figs. 6a, b). In addition, acrosyringium in the lesions skin also showed the protein expression (Fig. 6c), but not in healthy skin (Fig. 6e, f). The eccrine pore at the surface of skin showed weak positive staining locating (Fig. 6f, arrowhead). (Original magnifications: a, c, d, e: 40×, b, f: 100×).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199729&req=5

pone-0110677-g006: MCP-1 expression in PPP lesion skin and healthy skin.In lesion skin, strong expression of MCP-1 was detected around the PPP vesicle in the epidermis (Figs. 6a, b). In addition, acrosyringium in the lesions skin also showed the protein expression (Fig. 6c), but not in healthy skin (Fig. 6e, f). The eccrine pore at the surface of skin showed weak positive staining locating (Fig. 6f, arrowhead). (Original magnifications: a, c, d, e: 40×, b, f: 100×).
Mentions: The epidermis surrounding the PPP vesicle expressed the MCP-1 protein (Fig. 6a–c, e, f). No signal was detected from pre-immune mouse IgG (Fig. 6d).

Bottom Line: 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).Proteinase 3, which converts hCAP-18 to the active form (LL-37), was present in PPP-VF.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.

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.

Show MeSH
Related in: MedlinePlus