Role for Toll-like receptor (TLR) 4 on the deleterious effect of ultraviolet to suppress cutaneous immunity
| Project/Area Number |
16591112
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Nara Medical University |
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Principal Investigator |
NIIZEKI Hironori Nara Medical University, School of Medicine, Assistant Professor, 医学部, 教授 (10228124)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAGAWA Sachiko Nara Medical University, School of Medicine, Professor, 医学部, 教授 (30094626)
ASADA Hideo Nara Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (60252681)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Ultraviolet / TLR4 / Innate immunity / Contact hypersensitivity / Langerhans cell |
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| Research Abstract |
Ultraviolet (UV) decreases density of Langerhans cells (LCs) and impairs the induction of contact hypersensitivity (CH) in some strains of mice. However, in Toll-like receptor (TLR)4-deficient, C3H/HeJ (HeJ), hapten painted on UV-treated skin sensitizes well.
The purpose of this study is to determine the roles for TLR4 on the deleterious effects of UV to impair cutaneous immunity using lipopolysaccharide (LPS) to directly stimulate TLR4.
The abdominal skins of mice received 25 μg LPS intradermally. Two hours later, epidermal sheets were prepared and stained for Ia+ (Langerhans) cells. LCs from LPS-injected skin in C3H/HeN displayed altered morphology of LCs when compared with control or LPS-injected skin from HeJ, comparable with UV-exposed skin. We next determined the effect of anti-TNF antibodies on LPS effect. Anti-TNF antibodies abrogated the effect of LPS on density and morphology of LCs, indicating that TNF is an important mediator of the effects of LPS, as well as UV.
We next tested whether the effect of UV on induction of CH in MyD88 knockout (KO) mice and wild littermates (C57BL/6 background, B6). Panels of mice were exposed to UV (400 J/m^2/day) for 4 consecutive days. Within 30 mm of the last exposure, the exposed site was painted with 185 μg DNFB. The ears of these mice were challenged 5 days later and the ear swelling responses measured. We found that KO mice as well as B6 showed the intensity of CH when compared with (unexposed) controls, suggesting that the effect of UV on induction of CH is (TLR4-dependent but) MyD88-independent.
We finally tested whether LPS can restore the effect of UV on CH. LPS reversed the intensity of CH when LPS was injected either before or after UVB exposures, indicating that TLR4 signaling is capable of modulating the induction of CH. We concluded that TLR4 signaling is an important factor to alter cutaneous immunity.
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] Mosquito salivary gland extracts induce EBV-infected NK cell oncogenesis via CD4 T cells in patients with hypersensitivity to mosquito bites.2005
Author(s)
Asada H, Saito-Katsuragi M, Niizeki H, Yoshioka A, Suguri S, Isonokami M, Aoki T, Ishihara S, Tokura Y, Iwatsuki K, Miyagawa S
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Journal Title
J Invest Dermatol 125(5)
Pages: 956-961
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Mosquito salivary gland extracts induce EBV-infected NK cell oncoger CD4 T cells in patients with hypersensitivity to mosquito bites2005
Author(s)
Asada H, Saito-Katsuragi M, Niizeki H, Yoshioka A, Suguri S, Isonokami M, Aoki T, Ishihara S, Tokura Y, Iwatsuki K, Miyagawa S
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Journal Title
J Invest Dermatol 125(5)
Pages: 956-961
Related Report
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[Journal Article] Induction of macrophage migration inhibitory factor precedes the onset of acute tonsillitis.2004
Author(s)
Shimizu T, Niizeki H, Takeuchi O, Yamasaki Y, Inamoto N, Kusunoki Y, Kobayashi K, Abe R, Shimizu H, Nishikawa T, Hashiguchi K, Nishihira J.
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Journal Title
Mediators Inflamm 13
Pages: 293-295
Description
「研究成果報告書概要(欧文)」より
Related Report
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