Exacerbated and prolonged allergic and non-allergic inflammatory cutaneous reaction in mice with targeted interleukin-18 expression in the skin.
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-gamma, 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.
Kawase
Yusuke
Y
R&D Laboratories, Nippon Organon K.K., Osaka, Japan.
Hoshino
Tomoaki
T
Yokota
Koichi
K
Kuzuhara
Akemi
A
Kirii
Yasuyuki
Y
Nishiwaki
Eiji
E
Maeda
Yu
Y
Takeda
Junji
J
Okamoto
Masaki
M
Kato
Seiya
S
Imaizumi
Toshihiro
T
Aizawa
Hisamichi
H
Yoshino
Kohichiro
K
D000818:Animals; D019070:Cell Lineage / Q000276:immunology; D018925:Chemokines / Q000235:genetics; D003436:Croton Oil; D016207:Cytokines / Q000235:genetics; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D004431:Ear, External; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology*; D007509:Irritants; D053569:Keratin-15; D053555:Keratin-5; D015603:Keratinocytes / Q000473:pathology / Q000502:physiology; D007633:Keratins / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010853:Picryl Chloride; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000276:immunology* / Q000473:pathology
D018925:Chemokines; D016207:Cytokines; D020382:Interleukin-18; D007509:Irritants; C503940:KRT5 protein, human; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse; D012333:RNA, Messenger; D007633:Keratins; D003436:Croton Oil; D010853:Picryl Chloride