RESEARCH ON TRANSGENIC MICE OVEREXPRESSING CHEMOKINES IN EPIDERMAL KERATINOCYTES
| Project/Area Number |
17591160
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Dermatology
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
SAEKI Hidehisa The University of Tokyo, TOKYO UNIVERSITY HOSPITALDERMATOLOGY, ASSISTANT PROFESSOR (80235093)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | chemokine / transgenic mice / TARC / CCL17 / CTACK / CCL27 / contact hypersensitivity / CCR4 / CCR10 / atopic dermatitis / FITC / MDC(CCL22) |
|---|
| Research Abstract |
We created transgenic (Tg) mice where TARC/CCL17 is overexpressed in keratinocytes (KC). Th2-type contact hypersensitivity (CHS) was enhanced and Th1-type was suppressed in Tg mice. Increased number of CCR4^+ cells and mast cells infiltrated in Tg mice. IL-4 mRNA expression was higher and that of IFN-γ was lower in Tg mice in both acute (single application) and chronic(repeated application) CHS. Higher levels of serum IgE were observed in Tg mice after CHS. Numbers of CCR4^+ cells among peripheral blood mononuclear cells were increased in Tg mice challenged acutely on the trunk. Chronic irritation with croton oil induced dermatitis and elevation of serum IgE levels. TARC was thought to modify the inflammation caused by sensitizing reagents as well as irritant reagents by attracting CCR4^+ cells into the lesional skin and creating a Th2-dominant condition. AD-like conditions such as increased number of mast cells and elevated levels of serum IgE were observed. Thus, TARC may participate in the pathogenesis of skin diseases such as atopic dermatitis (AD) by regulating both allergic and irritant inflammation.
We also created Tg mice that constitutively produce CTACK/CCL27 in epidermal KC. Interestingly, only chronic CHS with fluorescein isothiocyanate (FITC; Th2-type reagent) was significantly enhanced in Tg mice compared to non Tg mice. Under this condition, the numbers of CCR10-positive cells, CCR4-positive cells were increased, and IL-4 mRNA expression was higher in the lesional skin of Tg mice. Increased number of mast cells and higher serum IgE levels were also observed. These results indicated that CTACK modified inflammation by attracting CCR10-positive and CCR4-positive cells into the lesional skin, and may participate in the pathogenesis of Th2 shifted skin diseases such as AD.
|
Report
(4 results)
Research Products
(19 results)
