| Project/Area Number |
09670613
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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 |
Respiratory organ internal medicine
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
HIYAMA Keiko Hiroshima Univ.Faculty of Medicine, Research Associate, 医学部, 助手 (60253069)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Hiroyuki Hiroshima Univ.Faculty of Medicine, Research Associate, 医学部・附属病院, 助手 (80274075)
ISHIOKA Shinichi Hiroshima Univ.Faculty of Medicine, Assistant Professor, 医学部, 講師 (10191868)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | telomerase / lymphocyte / asthma / sensitive / atopy / allergy / memory T cell / hTERT / 膠原病 |
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| Research Abstract |
In asthma, allergen-specific T lymphocytes are considered to play important roles in maintaining allergic potential, as well as in initiating and propagating allergic inflammation as effector cells. To elucidate the association of telomerase in these roles, we analyzed the upregulation of telomerase activity in allergen-specific T lymphocytes in atopic asthmatics who are sensitive to house dust mite (HDM). Peripheral blood mononuclear cells (PBMCs) were cultured with or without the stimulation of HDM for 7 days. Telomerase activity in the total lymphocytes and the CD4+CD45RO+ lymphocytes was measured using a telomeric repeat amplification protocol (TRAP) assay. While the freshly isolated PBMCs obtained from asthmatics and control subjects showed comparable low levels of telomerase activity, telomerase activity in the CD4+CD45RO+ T lymphocytes obtained from asthmatics was upregulated after the 1-week culture in the presence of HDM.Moreover, all asthmatics whose telomerase activity in lymphocytes was highly upregulated by the HDM stimulation had a history of atopic diseases in childhood. Thus, the upregulation of telomerase activity in memory T cells activated during allergen-specific immune responses might be associated with the enduring allergen-specific atopic propensity in asthmatics.
Then, we tried to suppress the telomerase activity in cultured EB-virus-transformed B lymphoblasts by peptide nucleic acids (PNA) having antisense sequence of the part of human telomerase reverse transcriptase (hTERT). Telomerase activity was not suppressed by the addition of PNA possibly by the low transduction efficiency. To overcome this problem, we next constructed an adenovirus vector with cytomegalovirus promoter which expresses antisense hTERT.Telomerase activity in cultured cancer cell lines was not suppressed by the addition of this vector, possibly due to the constructive problems.
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