| Project/Area Number |
14571291
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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 |
Thoracic surgery
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| Research Institution | Fukuoka University |
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Principal Investigator |
SHIRAKUSA Takayuki Fukuoka Univ., School of Medicine, Professor, 医学部, 教授 (20038863)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAISHI Takeshi Fukuoka Univ., School of Medicine, Assistant Professor, 医学部, 講師 (10216179)
KAWAHARA Katsunobu Fukuoka Univ., School of Medicine, Associate Professor, 医学部, 助教授 (80152990)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Lung transplantation / Transplant rejection / Cellular immunity / Interleukin-2 / Intracellular signal / Tyrphostin AG490 / Lung / Transplantatation / Rejection / Costimulation / Inducible costimulator / Transplantation / Inducible costimulator (ICOS) |
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| Research Abstract |
The JAK/STAT pathway, one of intracellular signals from IL-2 receptor (IL-2R), plays a critical role in T-cell development and function. Tyrphostin AG490 is a promising agent for the blockade of IL-2R signaling at the level of Jak3 kinase. A recent investigation indicates that AG490 efficiently blocks the Jak3 activity in T-cells.
To test the notion that inhibition of JAK3 may have an immunosuppressive potential, a 7-day course of i.p injection with 10mg/kg, 15mg/kg, and 20mg/kg of AG490 was used to inhibit the rejection of heterotopically transplanted Brown Norway (BN : RT1^n) lung allografts in F344 (RT1^<lvl>) recipients.
The progression of rejection was evaluated radiographically using a semiquantative grading system (Aeration Score : AS; 0=opaque→6=full aeration). Recipients were sacrificed on day 8, and the grade of rejection was histologically determined based on the LW.F of lung acute rejection (Rejection Score : RS; O=no rejection→4=severe rejection).
The AG490-treated recipients showed a significantly high AS in comparison to the untreated recipients on day 6. In addition, a significant suppression of rejection in the AG490-treated recipients was histologically confirmed in a dose dependent manner.
We conclude that the inhibition of the JAK/STAT pathway may allow for the efficient suppression of lung allograft rejection.
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