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ID 11680
Eprint ID
11680
フルテキストURL
K003303.pdf 62.9 KB
タイトル(別表記)
ヒスタミンH4受容体アゴニストは、抗原特異的ヒトT細胞応答においてH4アゴニスト作用以上の働きをする
著者
菅田 裕士 岡山大学
抄録
Histamine not only mediates immediate allergic reactions, it also regulates cellular immune responses. H4R is the most recently identified histamine receptor (HR). In the present study, we examined the in vitro effect of histamine and H4R agonists on the responses of human T cells to purified protein derivative from Mycobacterium tuberculosis (PPD) and to Cry j1, the major allergen of Cryptomeria japonica pollen. Dimaprit, clobenpropit and clozapine, which are H4R agonists, dose-dependently blocked both PPD-induced interferon-gamma and Cry j1-induced interleukin-5 production by both peripheral blood mononuclear cells (PBMCs) and antigen-specific T-cell lines. However, the addition of thioperamide, an H3R/H4R antagonist, as well as a mixture of d-chlropheniramine, famotidine and thioperamide, did not reverse the inhibition. Pretreatment of PBMCs with SQ22536 and 8-bromoadenosine-3',5'-cyclic monophosphorothioate, Rp-isomer, had varying abilities to reverse the inhibitory effects of H4R agonists, except for clobenpropit. Moreover, the addition of H4R agonists induced annexin-V expression on PBMCs, especially in CD19(+) and CD4(+) cells. cDNA microarray analysis revealed that, among 16,600 genes tested, increased expression following treatment with clozapine was seen in 0 x 8% of the genes, whereas decreased expression was seen in 3 x 0% of the genes. These results suggest that H4R agonists inhibit antigen-specific human T-cell responses, although H4R does not appear to be important for this effect. In addition, the present study indicated that there may be orphan receptors or HR subtypes which can bind dimaprit, clobenpropit and clozapine, and that can exert an inhibitory effect on antigen-specific cellular responses via a cAMP/cAMP-dependent protein kinase-dependent, apoptotic pathway.
キーワード
cytokine
histamine
H4R
human studies
T cell
備考
http://dx.doi.org/10.1111/j.1365-2567.2007.02574.x
発行日
2007-03-23
出版物タイトル
資料タイプ
学位論文
学位授与番号
甲第3303号
学位授与年月日
2007-03-23
学位・専攻分野
博士(医学)
授与大学
岡山大学
オフィシャル URL
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17346280&dopt=Abstract
言語
Japanese
論文のバージョン
none
査読
不明