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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

Cooperative role of TNF-α and IL-17 with IL-22 on S100A7 expression.(A, B) NHEKs were stimulated for 24 h with IL-22 or a combination of IL-22 plus IL-17A, TNF-α or IFN-γ. RNA was isolated from the cells and subjected to quantitative real-time PCR analysis for CCL5 (A) and S100A7 (B) expression were then analyzed using real-time PCR. Bars depict the mean ± S.D. (n = 6). **p < 0.01, ***p < 0.001 (one-way ANOVA).
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pone.0140750.g003: Cooperative role of TNF-α and IL-17 with IL-22 on S100A7 expression.(A, B) NHEKs were stimulated for 24 h with IL-22 or a combination of IL-22 plus IL-17A, TNF-α or IFN-γ. RNA was isolated from the cells and subjected to quantitative real-time PCR analysis for CCL5 (A) and S100A7 (B) expression were then analyzed using real-time PCR. Bars depict the mean ± S.D. (n = 6). **p < 0.01, ***p < 0.001 (one-way ANOVA).

Mentions: TNF-α and IFN-γ stimulation significantly increased CCL5 expression (Fig 3A) and IL-22 in combination with IL-17A or TNF-α augmented the effect of IL-22 on S100A7 expression (Fig 3B). These results clearly demonstrated both IL-17A and TNF-α are active. However, similar to SLURP1 expression, IFN-γ combined with IL-22 abolished the effect of IL-22 on S100A7 expression (Fig 3B). These results indicate that IFN-γ somehow affects IL-22-induced gene expression.


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)

Cooperative role of TNF-α and IL-17 with IL-22 on S100A7 expression.(A, B) NHEKs were stimulated for 24 h with IL-22 or a combination of IL-22 plus IL-17A, TNF-α or IFN-γ. RNA was isolated from the cells and subjected to quantitative real-time PCR analysis for CCL5 (A) and S100A7 (B) expression were then analyzed using real-time PCR. Bars depict the mean ± S.D. (n = 6). **p < 0.01, ***p < 0.001 (one-way ANOVA).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140750.g003: Cooperative role of TNF-α and IL-17 with IL-22 on S100A7 expression.(A, B) NHEKs were stimulated for 24 h with IL-22 or a combination of IL-22 plus IL-17A, TNF-α or IFN-γ. RNA was isolated from the cells and subjected to quantitative real-time PCR analysis for CCL5 (A) and S100A7 (B) expression were then analyzed using real-time PCR. Bars depict the mean ± S.D. (n = 6). **p < 0.01, ***p < 0.001 (one-way ANOVA).
Mentions: TNF-α and IFN-γ stimulation significantly increased CCL5 expression (Fig 3A) and IL-22 in combination with IL-17A or TNF-α augmented the effect of IL-22 on S100A7 expression (Fig 3B). These results clearly demonstrated both IL-17A and TNF-α are active. However, similar to SLURP1 expression, IFN-γ combined with IL-22 abolished the effect of IL-22 on S100A7 expression (Fig 3B). These results indicate that IFN-γ somehow affects IL-22-induced gene expression.

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