Interleukin 33 Is Induced by Tumor Necrosis Factor and Interferon in Keratinocytes and Contributes to Allergic Contact Dermatitis

Background: Interleukin (IL) 33, a novel member of the IL-1 family, is produced mainly by epithelial cells and endothelial cells in response to various types of stress, including necrosis. The effects of IL-33 on the immune cells involved in allergic contact dermatitis have recently been revealed in vitro. However, in vivo, the induction mechanism and function of IL-33 are not fully understood. Objectives: Our objectives were to investigate induction of IL-33 in keratinocytes and to evaluate the functions of IL-33 and its inducers in a murine model of allergic contact dermatitis. Material and Methods: KERTr cells, a human keratinocyte cell line, were cultured with various cytokines, including tumor necrosis factor (TNF) and interferon (IFN) . IL-33 expression was detected using quantitative reverse transcriptase polymerase chain reaction, immunocytochemistry, and Western blotting. The functions of IL-33, TNF, and IFNin allergic contact dermatitis were evaluated using a murine model. Results: TNFand IFNinduced expression of IL-33 mRNA and protein in KERTr cells. Blockade of IL-33 attenuated swelling in the ears of the experimental mice. Similar effects were noted for blockade of TNFand IFNin these mice. Conclusions: TNFand IFNinduce expression of IL-33, and IL-33 produced by keratinocytes contributes to allergic contact dermatitis. Blockade of IL-33, TNF, and IFNcould represent novel and potent strategies to treat allergic contact dermatitis.