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

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.

• Authors: Yasuhiro Moriwaki, Kiyoko Takada, Toshinori Nagasaki, Natsuki Kubo, Tomohiro Ishii, Kazuaki Kose, Taihei Kageyama, Shoutaro Tsuji, Koichiro Kawashima, Hidemi Misawa
• Journal: PloS one (PLoS One) Vol. 10 Issue 10 Pg. e0140750 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26474319 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoquinolines
• Antigens, Ly
• Interleukins
• SLURP-1 protein, mouse
• SLURP1 protein, human
• STAT3 Transcription Factor
• Urokinase-Type Plasminogen Activator
• Imiquimod
• interleukin-22

Topics

• Aminoquinolines (pharmacology)
• Animals
• Antigens, Ly (genetics, metabolism)
• Female
• Homeostasis (drug effects)
• Humans
• Imiquimod
• Interleukins (pharmacology)
• Keratinocytes (cytology, drug effects, metabolism)
• Mice
• Mice, Inbred BALB C
• Psoriasis (chemically induced, genetics, metabolism, microbiology)
• STAT3 Transcription Factor (metabolism)
• Skin (drug effects, metabolism, microbiology)
• Staphylococcus aureus (growth & development)
• Up-Regulation (drug effects)
• Urokinase-Type Plasminogen Activator (genetics, metabolism)