Tumour necrosis factor-α induces C-C motif chemokine ligand 5 production in canine keratinocytes.

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.

Case report: First isolation of Exophiala dermatitidis from subcutaneous phaeohyphomycosis in a cat.

Phaeohyphomycosis, which is caused by the opportunistic black yeast-like fungus Exophiala dermatitidis, has been reported in humans and dogs. However, no previous studies describing E. dermatitidis infections in cats have been published. Herein, we report a case of subcutaneous phaeohyphomycosis caused by E. dermatitidis. A 12-year-old, castrated male Japanese domestic short-haired cat presented with a solitary subcutaneous abscess on the left side of the neck, where an esophageal tube for force-feeding had been placed previously. The cat was diagnosed with hepatitis and was treated with prednisolone. The subcutaneous abscess was incised using a scalpel blade and the pus was excreted. The cytology of the pus revealed hyphae with neutrophil and macrophage infiltration. Although the cat was treated with oral itraconazole or an infusion of topical ketoconazole cream applied to the lesion, it died. The fungal culture of the pus specimen developed dark-green, waxy, smooth, yeast-like colonies. Sequencing of the internal transcribed spacer 1-4 regions of the ribosomal DNA of the pus specimen showed 100% identity with that of the standard strains of E. dermatitidis. Based on these results, the cat was diagnosed with subcutaneous phaeohyphomycosis caused by E. dermatitidis. The antifungal susceptibility test revealed that the fungus showed low or moderate susceptibility to the antifungal drugs examined, except for amphotericin B, which exhibited high in vitro antifungal activity. This is the first case report to provide definitive evidence of E. dermatitidis infection in cats and antifungal susceptibility test results against clinically isolated E. dermatitidis.

Toceranib phosphate and firocoxib-mediated partial response in a dog with advanced intranasal sarcoma.

A nine-year-old, castrated male mixed-breed dog presented with a three-month history of sneezing and stertorous breathing. Computed tomography revealed a soft tissue mass in the left nasal cavity with lysis of the cribriform plate. The mass was diagnosed as intranasal sarcoma based on histopathological analysis. The tumor cells were immunohistochemically positive for KIT and platelet-derived growth factor receptor α/ß and negative for vascular endothelial growth factor receptor 2 and cyclooxygenase-2. Treatment with toceranib phosphate (TOC) and firocoxib reduced the tumor size, which was defined as partial response (PR). After PR induction, TOC alone mediated survival for 205 days. This case report suggests that the combination of TOC and possibly firocoxib may be a therapeutic option for canine intranasal sarcoma.