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- Title
Tumour necrosis factor‐α induces C‐C motif chemokine ligand 5 production in canine keratinocytes.
- Authors
Takahashi, Kaho; Okazawa, Taiga; Shingaki, Tomoaki; Furuya, Keiko; Kimura, Junpei; Ohmori, Keitaro
- Abstract
Background: C‐C motif chemokine ligand (CCL)5 induces skin inflammation in healthy dogs. In addition, CCL5 is overexpressed in the skin of experimental models of canine atopic dermatitis (cAD). Tumour necrosis factor (TNF)‐α has been shown to be upregulated in cAD. However, it remains unclear whether TNF‐α induces CCL5 production in canine keratinocytes. Hypothesis/Objectives: To determine the effect of TNF‐α on CCL5 production in canine keratinocyte culture and investigate possible synergy with interferon (IFN)‐γ and interleukin (IL)‐4. Materials and Methods: CCL5 protein concentrations were measured by enzyme‐linked immunosorbent assay (ELISA) in the culture supernatant of a cell line of canine progenitor epidermal keratinocyte (CPEK) cells stimulated with TNF‐α with or without inhibitors of the TNF receptor signalling pathway. CCL5 protein concentrations also were measured in CPEK cells stimulated with TNF‐α in the absence or presence of IFN‐γ, a T‐helper (Th)1‐type cytokine, and/or IL‐4, a Th2‐type cytokine. Results: TNF‐α increased CCL5 production in CPEK cells in time‐ and dose‐dependent manners. Inhibitors of the TNF receptor signalling pathway diminished CCL5 production. Although neither IFN‐γ nor IL‐4 alone induced CCL5 production in CPEK cells, the combination of TNF‐α and IFN‐γ, and not IL‐4, synergistically enhanced CCL5 production in these cells. Conclusions and Clinical Relevance: TNF‐α may be involved in skin inflammation in dogs by promoting CCL5 production in keratinocytes. Furthermore, the synergistic effect of TNF‐α and IFN‐γ suggests that the local Th1‐type milieu may aggravate skin inflammation. Further studies are required to elucidate the role of TNF‐α‐induced CCL5 production of keratinocytes in the pathogenesis of cAD.
- Subjects
KERATINOCYTES; TUMOR necrosis factor receptors; SKIN inflammation; ENZYME-linked immunosorbent assay; ATOPIC dermatitis; KERATINOCYTE differentiation
- Publication
Veterinary Dermatology, 2024, Vol 35, Issue 2, p219
- ISSN
0959-4493
- Publication type
Article
- DOI
10.1111/vde.13227