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- Title
Exacerbated and Prolonged Allergic and Non-Allergic Inflammatory Cutaneous Reaction in Mice with Targeted Interleukin-18 Expression in the Skin.
- Authors
Kawase, Yusuke; Hoshino, Tomoaki; Yokota, Koichi; Kuzuhara, Akemi; Kirii, Yasuyuki; Nishiwaki, Eiji; Maeda, Yu; Takeda, Junji; Okamoto, Masaki; Kato, Seiya; Imaizumi, Toshihiro; Aizawa, Hisamichi; Yoshino, Kohichiro
- Abstract
Interleukin 18 induces both T helper 1 and T helper 2 cytokines, proinflammatory cytokines, chemokines, and IgE and IgG1 production. A role of interleukin 18 in inflammatory cutaneous reactions is still unclear, however. Here we generated keratin 5/interleukin 18 transgenic mice overexpressing mature murine interleukin 18 in the skin using a human keratin 5 promoter. In the contact hypersensitivity model, trinitrochlorobenzene elicited a stronger ear swelling in keratin 5/interleukin 18 transgenic mice compared with control littermate wild-type or immunoglobulin/interleukin 18 transgenic mice in which mature interleukin 18 was expressed by B and T cells under the control of the immunoglobulin promoter. Application of an irritant, croton oil, induced stronger and more sustained ear swelling in keratin 5/interleukin 18 transgenic mice than in immunoglobulin/interleukin 18 transgenic or wild-type mice. Repetitive topical application (weekly for six consecutive weeks) of trinitrochlorobenzene to their ears also elicited a stronger cutaneous inflammation in keratin 5/interleukin 18 transgenic mice than seen in immunoglobulin/interleukin 18 transgenic or wild-type mice. After these six trinitrochlorobenzene applications, the expression of interferon-γ, interleukin-4, and CCL20 mRNA in the ear tissue was increased and dermal changes, such as acanthosis and eosinophilic, neutrophilic, and mast cell infiltration, were greater in keratin 5/interleukin 18 transgenic mice than in wild-type mice. Furthermore, the repetitive application elicited a significant increase in serum IgE levels and the number of B cells in the draining lymph node in keratin 5/interleukin 18 transgenic mice. These results suggest that overexpression of interleukin 18 in the skin aggravates allergic and nonallergic cutaneous inflammation, which is accompanied by high expression of T helper 1 and T helper 2 cytokines and chemokines in the skin.
- Subjects
INTERLEUKINS; T cells; CYTOKINES
- Publication
Journal of Investigative Dermatology, 2003, Vol 121, Issue 3, p502
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1046/j.1523-1747.2003.12407.x