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Original Article


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


K Taniguchi,1,2 S Yamamoto,1 E Hitomi,1 Y Inada,1 Y Suyama,1 T Sugioka,2 Y Hamasaki1

1Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
2Community Medical Support Institute, Faculty of Medicine, Saga University, Saga, Japan

J Investig Allergol Clin Immunol 2013; Vol. 23(6): 428-434



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) a and interferon (IFN) g. IL-33 expression was detected using quantitative reverse transcriptase polymerase chain reaction, immunocytochemistry, and Western blotting. The functions of IL-33, TNF-a, and IFN-g in allergic contact dermatitis were evaluated using a murine model.

Results: TNF-a and IFN-g induced 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 TNF-a and IFN-g in these mice.

Conclusions: TNF-a and IFN-g induce expression of IL-33, and IL-33 produced by keratinocytes contributes to allergic contact dermatitis. Blockade of IL-33, TNF-a, and IFN-g could represent novel and potent strategies to treat allergic contact dermatitis.

Key words: Interleukin 33. Keratinocyte. Tumor necrosis factor a. Interferon g. Allergic contact dermatitis.