| Project/Area Number |
18K09536
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 57020:Oral pathobiological science-related
|
|---|
| Research Institution | Nagasaki University |
|---|
Principal Investigator |
Kadowaki Tomoko 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (70336080)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
筑波 隆幸 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30264055)
|
|---|
| Project Period (FY) |
2018-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | アレルギー / 細胞内小胞輸送 / 脱顆粒 / ケミカルメデイエーター / Rabタンパク質 / マスト細胞 / アレルギー反応 / 炎症反応 / アナフィラキシー / 免疫応答 / 炎症応答 / 細胞外分泌 / 小胞輸送 |
|---|
| Outline of Final Research Achievements |
Mast cells are responsible for anaphylaxis and allergy. Rab44 is a large Rab GTPase that contains a Rab GTPase domain and some additional N-terminal domains. Here we investigated the role of Rab44 in the physiology of mast cells and in anaphylaxis. Rab44 knockdown impaired degranulation of murine bone-marrow mast cells (BMMCs). Rab44-knockout mice exhibited diminished anaphylaxis, and Rab44-knockout BMMCs showed a decrease in histamine secretion. Confocal microscopic analysis of constitutively active Rab44 mutants showed their partial translocation from lysosomes to the plasma membrane. Treatment with a Ca2+ ionophore also induced the translocation of Rab44 from lysosomes into the plasma membrane and cytosol. Mechanistically, Rab44 interacted with VAMP8, which is a v-SNARE protein, to promote degranulation. Immunohistochemical studies indicated that Rab44 was detectable by only cells in the immune-related tissues, suggesting that it is closely involved in the inflammatory response.
|
| Academic Significance and Societal Importance of the Research Achievements |
近年、環境条件の悪化や生活様式の変化に伴うストレスによりアレルギー疾患に悩む人は増加している。アレルギー疾患の治療法としては「抗アレルギー薬」と呼ばれる一連の薬剤や吸入薬、外用のステロイド剤などが開発されているが、対症療法的が主流を占め、根治的な治療法の確立が期待されている。
我々の研究は、アレルギー反応の病態形成に直接関わる化学伝達物質の放出機構について新たな知見を示すものであり、今後の創薬標的としての可能性も秘めている。
|
