Abstract / Summary
Keratinocytes play a crucial role in the pathogenesis of canine atopic dermatitis (cAD). Tumor necrosis factor (TNF)-α, a proinflammatory cytokine, is highly expressed in the lesional skin of dogs with atopic dermatitis. Additionally, interferon (IFN)-γ, a T-helper (Th)1-type cytokine, and interleukin (IL)-13, a Th2-type cytokine, are also detected in the lesional skin during the acute and/or chronic phases of cAD. However, their effects on chemokine expression in canine keratinocytes remain unclear. This study investigated the effects of TNF-α on chemokine mRNA expression in canine keratinocytes and how IFN-γ or IL-13 modulates these responses. Canine progenitor epidermal keratinocyte (CPEK) cells were stimulated with TNF-α alone or in combination with IFN-γ or IL-13. Chemokine mRNA expression was analyzed by real-time PCR. TNF-α induced the mRNA expression of chemokines, including CCL2, CCL5, CCL17, CCL20, CCL22, CCL27, CCL28 , and CXCL8 . Co-stimulation with IFN-γ enhanced TNF-α-induced CCL5 and CXCL8 mRNA expression, but reduced TNF-α-induced CCL17, CCL20, CCL27 , and CCL28 mRNA expression. IL-13 augmented TNF-α-induced CCL17 mRNA expression, while suppressing TNF-α-induced CCL20 and CCL27 mRNA expression. IL-4, another Th2-type cytokine, was also confirmed to have effects similar to those of IL-13. These results indicate that TNF-α induces multiple chemokine genes in canine keratinocytes and that IFN-γ, IL-13, and IL-4 modulate this induction in a chemokine-specific manner, producing both enhancement and suppression. As these findings were obtained exclusively at the mRNA level in a canine keratinocyte cell line, their relevance to the pathogenesis and phases of cAD remains to be determined in vivo .