1999 Fiscal Year Final Research Report Summary
Analysis on the physiological role histamine in airway inflammation using knock-out mice
| Project/Area Number |
10670557
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Iwate Medical University |
|---|
Principal Investigator |
YAMAUCHI Kohei School of Medicine, Iwate Medical University, Associate Professor, 医学部, 助教授 (20200579)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OHTSU Hiroshi School of Medicine, Tohoku University, Associate Professor, 医学部, 講師 (60250742)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Keywords | Histamine / L-histidine decarboxylase / allergic reaction / knock-out mouse |
|---|
| Research Abstract |
1) Analysis on the mechanism of cell-specific expression of HDC gene L-Histidine decarboxylase (HDC) catalyzes the formation of histamine from L-histidine, and in hematopoletic lineages the gene is expressed only in mast cells and basophils. We attempted to discover how HDC gene expression is restricted in these cells. In cultured cell lines tested, only the mast cells (HMC-1) and basophils (KU-812-F) strongly transcribed the HDC gene but K562 or Hela did not. The promotor region of the HDC gene proved to be sensitive to Dnase in HDC-expressing cells. This sensitivity was proved to depend on the extent of methylation. CpG near transcriptional point in the promoter region of HDC gene in Hela and K562 was almost methylated, in contrast, that was not in HMC-1 or KU-812-F. These results imply that alteration of DNA methylation is one of the mechanisms regulating cell-specific expression of the HDC gene.
2) Analysis on allergic inflammation in HDC gene knock-out mice To elucidate the role of histamine in allergic reactions, we made knock-out mice which HDC gene was destructed. These mice are not capable to make histamine and are useful as the experimental model lacking histamine. Using these mice, we analyzed allergic responses and compared them to those in wild type mice. We measured exudation from capillaries in skin after exposure to antigen in sensitized HDC knock-out mice with ovalbumin. The exudation was calculated from amount Evans Blue in tissues, which was injected into vessels before. Result demonstrated that no exudation occurred in immediate allergic reaction in knock out mouse. After administrating food containing histamine, knock-out mice showed exudation in immediate allergic reaction. These results clearly indicated that exudation from vessels in allergic reaction was caused by histamine.
|
-
-
-
-
-
-
-
-
[Publications] Maeda K, Taniguchi H, Ohno I, Ohtsu H, Yamauchi K, Sakurai E, Tanno Y,.Butterfield JH, Watanabe T, Shirato K.: "Induction of L-histidine decarboxylase in a human mast cell line, HMC-1."Exp Hematol.. 26. 325-331 (1998)
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
[Publications] 9. Heinzman A, Mao X-Q, Akaiawa M, Kreomer RE, Gao P-S, Ohshima K, Umeshita R, Abe Y, Braun S, Yamashita T, Roberts MH, Sugimoto R, Arima K, Arinobu Y, Yu B, Kruse S, Enomoto T, Dake Y, Kawai M, Shimazu S, Sasaki S, Adra CN, Kitaichi M, lnoue H, Yamauchi K, Tomichi N, Kurimoto F, Hamasaki N, Hopkin JM, Izuhara K, Shirakawa T, Deichmann KA.: "Genetic variants of IL-13 signaling and human asthma and atopy."Human Molecular Genetics.. (in press). (2000)
Description
「研究成果報告書概要(欧文)」より
