Limits...
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

IMQ-induced psoriatic mouse skin has an abundance of SLURP1.IMQ or control cream was applied daily to the shaved backs for BALB/c mice. (A) Phenotypical presentation of mouse back skin after 2 or 4 days of IMQ treatment. (B) Immunofluorescent staining of vehicle or IMQ cream-treated mouse skin using an anti-SLURP1 antibody. Dashed lines indicate the border between the epidermis and dermis. Scale bars = 50 μm. The experiments were repeated six times with similar results. (C) Quantification of IL-22 and SLURP1 mRNA expression in skin from mice treated for 2 days with IMQ. Bars depict the mean ± S.D. (n = 6) of fold-changes in mRNA copy number normalized to GPADH and quantified relative to control. *p < 0.05, **p < 0.01 vs. control (Student’s t-test).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4608685&req=5

pone.0140750.g001: IMQ-induced psoriatic mouse skin has an abundance of SLURP1.IMQ or control cream was applied daily to the shaved backs for BALB/c mice. (A) Phenotypical presentation of mouse back skin after 2 or 4 days of IMQ treatment. (B) Immunofluorescent staining of vehicle or IMQ cream-treated mouse skin using an anti-SLURP1 antibody. Dashed lines indicate the border between the epidermis and dermis. Scale bars = 50 μm. The experiments were repeated six times with similar results. (C) Quantification of IL-22 and SLURP1 mRNA expression in skin from mice treated for 2 days with IMQ. Bars depict the mean ± S.D. (n = 6) of fold-changes in mRNA copy number normalized to GPADH and quantified relative to control. *p < 0.05, **p < 0.01 vs. control (Student’s t-test).

Mentions: IMQ-treated mice develop a psoriasis-like skin disorder [25]. We assessed SLURP1 expression in skin from the backs of mice treated with IMQ for 2 or 4 consecutive days. As shown in Fig 1A, we found that IMQ-treated skin developed signs of erythema, scaling and thickening over the course of treatment. Acanthosis is caused by keratinocyte hyperproliferation and scaling is caused by altered epidermal differentiation; both are seen in psoriatic skin lesions and were observed in the IMQ-treated mice (data not shown). Within the psoriasis-like skin lesions, SLURP1 protein expression was significantly increased in hyperproliferative keratinocytes (Fig 1B), and quantitative real-time PCR revealed corresponding elevation of SLURP1 mRNA expression (Fig 1C). In addition, the induction of IL-22, which appears to contribute to keratinocyte proliferation and epidermal hyperplasia, was also detected in the same skin samples (Fig 1C). The result in Fig 1B was highly reproducible, as indicated by the same results with other five mice (S1 Fig).


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)

IMQ-induced psoriatic mouse skin has an abundance of SLURP1.IMQ or control cream was applied daily to the shaved backs for BALB/c mice. (A) Phenotypical presentation of mouse back skin after 2 or 4 days of IMQ treatment. (B) Immunofluorescent staining of vehicle or IMQ cream-treated mouse skin using an anti-SLURP1 antibody. Dashed lines indicate the border between the epidermis and dermis. Scale bars = 50 μm. The experiments were repeated six times with similar results. (C) Quantification of IL-22 and SLURP1 mRNA expression in skin from mice treated for 2 days with IMQ. Bars depict the mean ± S.D. (n = 6) of fold-changes in mRNA copy number normalized to GPADH and quantified relative to control. *p < 0.05, **p < 0.01 vs. control (Student’s t-test).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140750.g001: IMQ-induced psoriatic mouse skin has an abundance of SLURP1.IMQ or control cream was applied daily to the shaved backs for BALB/c mice. (A) Phenotypical presentation of mouse back skin after 2 or 4 days of IMQ treatment. (B) Immunofluorescent staining of vehicle or IMQ cream-treated mouse skin using an anti-SLURP1 antibody. Dashed lines indicate the border between the epidermis and dermis. Scale bars = 50 μm. The experiments were repeated six times with similar results. (C) Quantification of IL-22 and SLURP1 mRNA expression in skin from mice treated for 2 days with IMQ. Bars depict the mean ± S.D. (n = 6) of fold-changes in mRNA copy number normalized to GPADH and quantified relative to control. *p < 0.05, **p < 0.01 vs. control (Student’s t-test).
Mentions: IMQ-treated mice develop a psoriasis-like skin disorder [25]. We assessed SLURP1 expression in skin from the backs of mice treated with IMQ for 2 or 4 consecutive days. As shown in Fig 1A, we found that IMQ-treated skin developed signs of erythema, scaling and thickening over the course of treatment. Acanthosis is caused by keratinocyte hyperproliferation and scaling is caused by altered epidermal differentiation; both are seen in psoriatic skin lesions and were observed in the IMQ-treated mice (data not shown). Within the psoriasis-like skin lesions, SLURP1 protein expression was significantly increased in hyperproliferative keratinocytes (Fig 1B), and quantitative real-time PCR revealed corresponding elevation of SLURP1 mRNA expression (Fig 1C). In addition, the induction of IL-22, which appears to contribute to keratinocyte proliferation and epidermal hyperplasia, was also detected in the same skin samples (Fig 1C). The result in Fig 1B was highly reproducible, as indicated by the same results with other five mice (S1 Fig).

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