Interleukin 33 is induced by tumor necrosis factor alpha and interferon gamma 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.


OBJECTIVE
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.


METHODS
KERTr cells, a human keratinocyte cell line, were cultured with various cytokines, including tumor necrosis factor (TNF) alpha and interferon (IFN) gamma. 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-y in allergic contact dermatitis were evaluated using a murine model.


RESULTS
TNF-alpha and IFN-gamma 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-alpha and IFN-gamma in these mice.


CONCLUSIONS
TNF-alpha and IFN-gamma induce expression of IL-33, and IL-33 produced by keratinocytes contributes to allergic contact dermatitis. Blockade of IL-33, TNF-alpha, and IFN-gamma could represent novel and potent strategies to treat allergic contact dermatitis.
Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan.
K
K
Taniguchi
Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan.
S
S
Yamamoto
Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan.
E
E
Hitomi
Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan.
Y
Y
Inada
Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan.
Y
Y
Suyama
Community Medical Support Institute, Faculty of Medicine, Saga University, Saga, Japan.
T
T
Sugioka
Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan.
Y
Y
Hamasaki
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma