Toll-like receptor signaling induces the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes

Saeko Sugimoto, Shin Morizane, Hayato Nomura, Mina Kobashi, Satoru Sugihara, Keiji Iwatsuki

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background: Lympho-epithelial Kazal-type inhibitor (LEKTI) tightly controls the activities of serine proteases such as kallikrein-related peptidase (KLK) 5 and KLK7 in the epidermis. LEKTI is known to be an essential molecule for the epidermal skin barrier, as demonstrated by SPINK5 nonsense mutation, which results in Netherton syndrome. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns or damage-associated molecular patterns and produce inflammatory cytokines, chemokines, and antimicrobial peptides. However, the effect of TLR signaling on the expression of LEKTI is not clear. Objective: To investigate whether TLR signaling can affect expression of LEKTI in epidermal keratinocytes. Methods: We stimulated a panel of TLR ligands and investigated the expression of LEKTI in normal human epidermal keratinocytes (NHEKs). We further measured trypsin or chymotrypsin-like serine protease activity in NHEK cultured media under stimulation with TLR3 ligand, poly (I:C). Immunostaining for LEKTI was performed using skin samples from skin infectious diseases. Results: TLR1/2, 3, 5, and 2/6 ligands induced the expression of LEKTI in NHEKs. The trypsin or chymotrypsin-like serine protease activity in NHEKs was up-regulated with the stimulation of poly (I:C). The gene expressions of KLK6, KLK10, KLK11, and KLK13 were also increased by poly (I:C). An immunohistochemical analysis demonstrated that the expression of LEKTI was up-regulated in the lesions of varicella, pyoderma, and rosacea. Conclusions: TLR signaling induces the expression of LEKTI in epidermal keratinocytes, which might contribute to the control of aberrant serine protease activities in inflammatory skin diseases.

Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalJournal of dermatological science
Volume92
Issue number2
DOIs
Publication statusPublished - Nov 2018

Keywords

  • Epidermal keratinocytes
  • Lympho-epithelial Kazal-type inhibitor
  • Serine protease inhibitor
  • Toll-like receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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