2. Academic Validation
  3. Toll-like receptor 2 activation induces C-C motif chemokine ligand 5 production in canine keratinocytes

Toll-like receptor 2 activation induces C-C motif chemokine ligand 5 production in canine keratinocytes

  • Vet Dermatol. 2025 Apr;36(2):117-126. doi: 10.1111/vde.13330.
Kaho Takahashi 1,  Rina Yoshimatsu 2,  Yuzuki Kaida 2,  Takehiro Hasegawa 1 3,  Keitaro Ohmori 1 2 4
Affiliations

Affiliations

  • 1 Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
  • 2 Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
  • 3 Kugenuna-Kaigan Animal Hospital, Fujisawa, Kanagawa, Japan.
  • 4 Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
PMID: 39973011 DOI: 10.1111/vde.13330
Abstract

Background: Toll-like Receptor 2 (TLR2) in keratinocytes can be activated by Staphylococcus spp. that are frequently detected on the skin of dogs with atopic dermatitis (AD). C-C motif chemokine ligand 5 (CCL5) produced by keratinocytes has been considered to be involved in the pathogenesis of canine AD (cAD). However, whether TLR2 activation induces CCL5 production in canine keratinocytes remains unclear.

Hypothesis/objectives: To elucidate the effect of TLR2 agonists on CCL5 production in canine keratinocytes, possible synergy with interferon (IFN)-γ, interleukin (IL)-13 or IL-4 and underlying mechanisms.

Materials and methods: Canine progenitor epidermal keratinocyte (CPEK) cells were stimulated with TLR2 agonists with or without inhibitors of the TLR2 signalling pathway or IFN-γ, a T-helper (Th)1-type cytokine and/or IL-13 or IL-4, a Th2-type cytokine. CCL5 protein concentrations in the culture supernatant were measured by enzyme-linked immunosorbent assay. Additionally, TLR2 mRNA expression was measured by Real-Time PCR in CPEK cells stimulated with IFN-γ.

Results: TLR2 agonists increased CCL5 production in CPEK cells. Inhibitors of the TLR2 signalling pathway suppressed CCL5 production. IFN-γ, but not IL-13 or IL-4, synergistically enhanced TLR2 agonist-induced CCL5 production. IFN-γ partially increased TLR2 mRNA expression in CPEK cells.

Conclusions and clinical relevance: TLR2 activation by Staphylococcus spp. may produce CCL5 in canine keratinocytes, thereby recruiting immune cells into the skin of dogs with AD. During the Th1-activated chronic phase of cAD, where TLR2 expression may be partially upregulated, Staphylococcus spp. may exacerbate skin inflammation. Further studies are warranted to determine the clinical significance and mechanisms of skin bacteria-mediated CCL5 production in keratinocytes.

Keywords

C‐C motif chemokine ligand 5; canine atopic dermatitis; interferon‐γ; keratinocyte; toll‐like receptor 2.

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