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IL-22/STAT3-Induced Increases in SLURP1 Expression within Psoriatic Lesions Exerts Antimicrobial Effects against Staphylococcus aureus.

Moriwaki Y, Takada K, Nagasaki T, Kubo N, Ishii T, Kose K, Kageyama T, Tsuji S, Kawashima K, Misawa H - PLoS ONE (2015)

Bottom Line: In NHEKs stimulated with the inflammatory cytokines IL-17, IL-22 and TNF-α, which are reportedly expressed in psoriatic lesions, SLURP1 mRNA expression was significantly up-regulated by IL-22 but not the other two cytokines.The stimulatory effect of IL-22 was completely suppressed in NHEKs treated with a STAT3 inhibitor or transfected with siRNA targeting STAT3.SLURP1 significantly suppressed the growth of S. aureus.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.

ABSTRACT

Background: SLURP1 is the causal gene for Mal de Meleda (MDM), an autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma and transgressive keratosis. Moreover, although SLURP1 likely serves as an important proliferation/differentiation factor in keratinocytes, the possible relation between SLURP1 and other skin diseases, such as psoriasis and atopic dermatitis, has not been studied, and the pathophysiological control of SLURP1 expression in keratinocytes is largely unknown.

Objectives: Our aim was to examine the involvement of SLURP1 in the pathophysiology of psoriasis using an imiquimod (IMQ)-induced psoriasis model mice and normal human epidermal keratinocytes (NHEKs).

Results: SLURP1 expression was up-regulated in the skin of IMQ-induced psoriasis model mice. In NHEKs stimulated with the inflammatory cytokines IL-17, IL-22 and TNF-α, which are reportedly expressed in psoriatic lesions, SLURP1 mRNA expression was significantly up-regulated by IL-22 but not the other two cytokines. The stimulatory effect of IL-22 was completely suppressed in NHEKs treated with a STAT3 inhibitor or transfected with siRNA targeting STAT3. Because IL-22 induces production of antimicrobial proteins in epithelial cells, the antibacterial activity of SLURP1 was assessed against Staphylococcus aureus (S. aureus), which is known to be associated with disease severity in psoriasis. SLURP1 significantly suppressed the growth of S. aureus.

Conclusions: These results indicate SLURP1 participates in pathophysiology of psoriasis by regulating keratinocyte proliferation and differentiation, and by suppressing the growth of S. aureus.

No MeSH data available.


Related in: MedlinePlus

SLURP1 exhibits an antibacterial activity against S. aureus.Mid-exponential growth phase S. aureus amd E. coli were incubated for 18 h with α-defensin2, magainin1 or rhSLURP1 purified from culture supernatants. After the incubation, bacterial proliferation was assessed based on the change in the OD620. The results are presented as percentages of growth relative to the untreated control. This assay was repeated in six independent experiments performed in triplicates. ***p < 0.001 (one-way ANOVA).
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pone.0140750.g005: SLURP1 exhibits an antibacterial activity against S. aureus.Mid-exponential growth phase S. aureus amd E. coli were incubated for 18 h with α-defensin2, magainin1 or rhSLURP1 purified from culture supernatants. After the incubation, bacterial proliferation was assessed based on the change in the OD620. The results are presented as percentages of growth relative to the untreated control. This assay was repeated in six independent experiments performed in triplicates. ***p < 0.001 (one-way ANOVA).

Mentions: IL-22 induces production of various AMPs, including β-defensin2, S100A7 and LL37, in regions of skin inflammation [23,24]. Because it has been reported that prostate and testis expressed protein (PATE), which is a secreted protein containing a Ly6 domain, has antibacterial activity [29], we investigated the antibacterial activity of partially purified rhSLURP1 secreted from SLURP1-transfected RK13 cells. As shown in Fig 5, SLURP1 dose dependently suppressed proliferation of the gram-positive bacterium S. aureus but not gram-negative bacterium E. coli. Although antibacterial activity of α-defensin2 to gram-negative bacterium E. coli was quite high, the suppressive effect of α-defensin2 on S. aureus proliferation was almost similar to that of SLURP1 (Fig 5). Magainin1 which does not kill gram-positive bacteria had no effect on proliferation of S. aureus [30], however magainin1 significantly suppressed proliferation of gram-negative bacterium E. coli at the same dose used for gram-positive bacteria (Fig 5). These results clearly demonstrate that SLURP1 is effective in suppression of proliferation in the gram-positive bacterium S. aureus but not gram-negative bacterium E. coli. More concentration of SLURP1 protein may completely suppress the proliferation of S. aureus, however the physiological concentration of SLURP1 has been reported around 10 ng/ml [28].


IL-22/STAT3-Induced Increases in SLURP1 Expression within Psoriatic Lesions Exerts Antimicrobial Effects against Staphylococcus aureus.

Moriwaki Y, Takada K, Nagasaki T, Kubo N, Ishii T, Kose K, Kageyama T, Tsuji S, Kawashima K, Misawa H - PLoS ONE (2015)

SLURP1 exhibits an antibacterial activity against S. aureus.Mid-exponential growth phase S. aureus amd E. coli were incubated for 18 h with α-defensin2, magainin1 or rhSLURP1 purified from culture supernatants. After the incubation, bacterial proliferation was assessed based on the change in the OD620. The results are presented as percentages of growth relative to the untreated control. This assay was repeated in six independent experiments performed in triplicates. ***p < 0.001 (one-way ANOVA).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608685&req=5

pone.0140750.g005: SLURP1 exhibits an antibacterial activity against S. aureus.Mid-exponential growth phase S. aureus amd E. coli were incubated for 18 h with α-defensin2, magainin1 or rhSLURP1 purified from culture supernatants. After the incubation, bacterial proliferation was assessed based on the change in the OD620. The results are presented as percentages of growth relative to the untreated control. This assay was repeated in six independent experiments performed in triplicates. ***p < 0.001 (one-way ANOVA).
Mentions: IL-22 induces production of various AMPs, including β-defensin2, S100A7 and LL37, in regions of skin inflammation [23,24]. Because it has been reported that prostate and testis expressed protein (PATE), which is a secreted protein containing a Ly6 domain, has antibacterial activity [29], we investigated the antibacterial activity of partially purified rhSLURP1 secreted from SLURP1-transfected RK13 cells. As shown in Fig 5, SLURP1 dose dependently suppressed proliferation of the gram-positive bacterium S. aureus but not gram-negative bacterium E. coli. Although antibacterial activity of α-defensin2 to gram-negative bacterium E. coli was quite high, the suppressive effect of α-defensin2 on S. aureus proliferation was almost similar to that of SLURP1 (Fig 5). Magainin1 which does not kill gram-positive bacteria had no effect on proliferation of S. aureus [30], however magainin1 significantly suppressed proliferation of gram-negative bacterium E. coli at the same dose used for gram-positive bacteria (Fig 5). These results clearly demonstrate that SLURP1 is effective in suppression of proliferation in the gram-positive bacterium S. aureus but not gram-negative bacterium E. coli. More concentration of SLURP1 protein may completely suppress the proliferation of S. aureus, however the physiological concentration of SLURP1 has been reported around 10 ng/ml [28].

Bottom Line: In NHEKs stimulated with the inflammatory cytokines IL-17, IL-22 and TNF-α, which are reportedly expressed in psoriatic lesions, SLURP1 mRNA expression was significantly up-regulated by IL-22 but not the other two cytokines.The stimulatory effect of IL-22 was completely suppressed in NHEKs treated with a STAT3 inhibitor or transfected with siRNA targeting STAT3.SLURP1 significantly suppressed the growth of S. aureus.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.

ABSTRACT

Background: SLURP1 is the causal gene for Mal de Meleda (MDM), an autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma and transgressive keratosis. Moreover, although SLURP1 likely serves as an important proliferation/differentiation factor in keratinocytes, the possible relation between SLURP1 and other skin diseases, such as psoriasis and atopic dermatitis, has not been studied, and the pathophysiological control of SLURP1 expression in keratinocytes is largely unknown.

Objectives: Our aim was to examine the involvement of SLURP1 in the pathophysiology of psoriasis using an imiquimod (IMQ)-induced psoriasis model mice and normal human epidermal keratinocytes (NHEKs).

Results: SLURP1 expression was up-regulated in the skin of IMQ-induced psoriasis model mice. In NHEKs stimulated with the inflammatory cytokines IL-17, IL-22 and TNF-α, which are reportedly expressed in psoriatic lesions, SLURP1 mRNA expression was significantly up-regulated by IL-22 but not the other two cytokines. The stimulatory effect of IL-22 was completely suppressed in NHEKs treated with a STAT3 inhibitor or transfected with siRNA targeting STAT3. Because IL-22 induces production of antimicrobial proteins in epithelial cells, the antibacterial activity of SLURP1 was assessed against Staphylococcus aureus (S. aureus), which is known to be associated with disease severity in psoriasis. SLURP1 significantly suppressed the growth of S. aureus.

Conclusions: These results indicate SLURP1 participates in pathophysiology of psoriasis by regulating keratinocyte proliferation and differentiation, and by suppressing the growth of S. aureus.

No MeSH data available.


Related in: MedlinePlus