TNF-α and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes

Satoru Sugihara, S. Sugimoto, Kota Tachibana, Mina Kobashi, Hayato Nomura, Tomoko Miyake, Youji Hirai, Osamu Yamasaki, Shin Morizane

Research output: Contribution to journalArticle

Abstract

Background: Serine proteases have important roles in skin barrier function and desquamation, and the aberrant expression or the dysfunction of serine proteases is associated with the pathogenesis of skin diseases. Serine protease activities are tightly regulated by serine proteases such as kallikrein-related peptidases (KLKs) and serine protease inhibitors such as lympho-epithelial Kazal-type related inhibitor (LEKTI). For a better understating of diseases’ pathogenesis, the regulation mechanism of serine proteases and the inhibitors’ expression in epidermal keratinocytes must be clarified. Objectives: To investigate the effects of the cytokines on the expression of LEKTI in epidermal keratinocytes. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with panels of inflammatory cytokines. The expression of serine protease inhibitors was analyzed using quantitative real-time PCR and ELISA. LEKTI expression in normal human skin and lesions from psoriasis or atopic dermatitis (AD) were analyzed by immunohistochemically and tape-stripping. Trypsin- and chymotrypsin-like serine protease activities in culture supernatants were measured by using specific substrates. Results: TNF-α and IL-17A significantly induced the expression of LEKTI in NHEKs. The immunohistochemical and tape-stripping analysis revealed that psoriatic skin lesions had higher LEKTI expression compared to normal skin and AD lesions. Trypsin- and chymotrypsin-like protease activities in the culture media were upregulated 3–5 days later but attenuated 6–7 days later period by these cytokines. Conclusions: In epidermal keratinocytes, the Th1&Th17 cytokines TNF-α and IL-17A induce the expression of serine protease inhibitor LEKTI, and it might occur to suppress the increase in the serine protease activities under inflammation.

Original languageEnglish
JournalJournal of dermatological science
DOIs
Publication statusAccepted/In press - Jan 1 2019

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Interleukin-17
Serine Proteases
Keratinocytes
Serine Proteinase Inhibitors
Skin
Chymases
Cytokines
Atopic Dermatitis
Tapes
Kallikreins
Psoriasis
Skin Diseases
Trypsin
Culture Media
Real-Time Polymerase Chain Reaction
Peptide Hydrolases
Enzyme-Linked Immunosorbent Assay
Inflammation
Substrates

Keywords

  • Epidermal keratinocyte
  • IL-17A
  • Lympho-epithelial Kazal-type inhibitor
  • Serine protease inhibitor
  • TNF-α

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

TNF-α and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes. / Sugihara, Satoru; Sugimoto, S.; Tachibana, Kota; Kobashi, Mina; Nomura, Hayato; Miyake, Tomoko; Hirai, Youji; Yamasaki, Osamu; Morizane, Shin.

In: Journal of dermatological science, 01.01.2019.

Research output: Contribution to journalArticle

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title = "TNF-α and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes",
abstract = "Background: Serine proteases have important roles in skin barrier function and desquamation, and the aberrant expression or the dysfunction of serine proteases is associated with the pathogenesis of skin diseases. Serine protease activities are tightly regulated by serine proteases such as kallikrein-related peptidases (KLKs) and serine protease inhibitors such as lympho-epithelial Kazal-type related inhibitor (LEKTI). For a better understating of diseases’ pathogenesis, the regulation mechanism of serine proteases and the inhibitors’ expression in epidermal keratinocytes must be clarified. Objectives: To investigate the effects of the cytokines on the expression of LEKTI in epidermal keratinocytes. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with panels of inflammatory cytokines. The expression of serine protease inhibitors was analyzed using quantitative real-time PCR and ELISA. LEKTI expression in normal human skin and lesions from psoriasis or atopic dermatitis (AD) were analyzed by immunohistochemically and tape-stripping. Trypsin- and chymotrypsin-like serine protease activities in culture supernatants were measured by using specific substrates. Results: TNF-α and IL-17A significantly induced the expression of LEKTI in NHEKs. The immunohistochemical and tape-stripping analysis revealed that psoriatic skin lesions had higher LEKTI expression compared to normal skin and AD lesions. Trypsin- and chymotrypsin-like protease activities in the culture media were upregulated 3–5 days later but attenuated 6–7 days later period by these cytokines. Conclusions: In epidermal keratinocytes, the Th1&Th17 cytokines TNF-α and IL-17A induce the expression of serine protease inhibitor LEKTI, and it might occur to suppress the increase in the serine protease activities under inflammation.",
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T1 - TNF-α and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes

AU - Sugihara, Satoru

AU - Sugimoto, S.

AU - Tachibana, Kota

AU - Kobashi, Mina

AU - Nomura, Hayato

AU - Miyake, Tomoko

AU - Hirai, Youji

AU - Yamasaki, Osamu

AU - Morizane, Shin

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Serine proteases have important roles in skin barrier function and desquamation, and the aberrant expression or the dysfunction of serine proteases is associated with the pathogenesis of skin diseases. Serine protease activities are tightly regulated by serine proteases such as kallikrein-related peptidases (KLKs) and serine protease inhibitors such as lympho-epithelial Kazal-type related inhibitor (LEKTI). For a better understating of diseases’ pathogenesis, the regulation mechanism of serine proteases and the inhibitors’ expression in epidermal keratinocytes must be clarified. Objectives: To investigate the effects of the cytokines on the expression of LEKTI in epidermal keratinocytes. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with panels of inflammatory cytokines. The expression of serine protease inhibitors was analyzed using quantitative real-time PCR and ELISA. LEKTI expression in normal human skin and lesions from psoriasis or atopic dermatitis (AD) were analyzed by immunohistochemically and tape-stripping. Trypsin- and chymotrypsin-like serine protease activities in culture supernatants were measured by using specific substrates. Results: TNF-α and IL-17A significantly induced the expression of LEKTI in NHEKs. The immunohistochemical and tape-stripping analysis revealed that psoriatic skin lesions had higher LEKTI expression compared to normal skin and AD lesions. Trypsin- and chymotrypsin-like protease activities in the culture media were upregulated 3–5 days later but attenuated 6–7 days later period by these cytokines. Conclusions: In epidermal keratinocytes, the Th1&Th17 cytokines TNF-α and IL-17A induce the expression of serine protease inhibitor LEKTI, and it might occur to suppress the increase in the serine protease activities under inflammation.

AB - Background: Serine proteases have important roles in skin barrier function and desquamation, and the aberrant expression or the dysfunction of serine proteases is associated with the pathogenesis of skin diseases. Serine protease activities are tightly regulated by serine proteases such as kallikrein-related peptidases (KLKs) and serine protease inhibitors such as lympho-epithelial Kazal-type related inhibitor (LEKTI). For a better understating of diseases’ pathogenesis, the regulation mechanism of serine proteases and the inhibitors’ expression in epidermal keratinocytes must be clarified. Objectives: To investigate the effects of the cytokines on the expression of LEKTI in epidermal keratinocytes. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with panels of inflammatory cytokines. The expression of serine protease inhibitors was analyzed using quantitative real-time PCR and ELISA. LEKTI expression in normal human skin and lesions from psoriasis or atopic dermatitis (AD) were analyzed by immunohistochemically and tape-stripping. Trypsin- and chymotrypsin-like serine protease activities in culture supernatants were measured by using specific substrates. Results: TNF-α and IL-17A significantly induced the expression of LEKTI in NHEKs. The immunohistochemical and tape-stripping analysis revealed that psoriatic skin lesions had higher LEKTI expression compared to normal skin and AD lesions. Trypsin- and chymotrypsin-like protease activities in the culture media were upregulated 3–5 days later but attenuated 6–7 days later period by these cytokines. Conclusions: In epidermal keratinocytes, the Th1&Th17 cytokines TNF-α and IL-17A induce the expression of serine protease inhibitor LEKTI, and it might occur to suppress the increase in the serine protease activities under inflammation.

KW - Epidermal keratinocyte

KW - IL-17A

KW - Lympho-epithelial Kazal-type inhibitor

KW - Serine protease inhibitor

KW - TNF-α

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