1996 Fiscal Year Final Research Report Summary
A ROLE OF CYTOKINE IN PROGRESSION OF HEART FAILRE
| Project/Area Number |
07670750
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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 |
Circulatory organs internal medicine
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| Research Institution | Yamagata University School of Medicine |
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Principal Investigator |
YAMAGUCHI Seiji Yamagata Univ.Sch.of Med., Instructor, 医学部, 講師 (30239892)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAKABE Masanori Yamagata Univ.Sch.of Med., Instructor, 医学部, 助手 (10241697)
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| Project Period (FY) |
1995 – 1996
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| Keywords | CONGESTIVE HEART FAILURE / TUMOR NECROSIS FACTOR (TNF) / SOLUBLE TNF RECEPTORS / CYTOKINE |
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| Research Abstract |
TNFalpha exerts its functions by binding to two specific receptors (TNF-RI and TNF-RII). The extracellular domains of TNF-RI and-RII are proteolytically cleaved (sTNF-RI and sTNF-RII) and neutralize the effects of TNF alpha. We investigated the surface and gene expressions of TNF-RII and the shedding of TNF-RII on mononulear leukocytes in patients with congestive heart failure (CHF). Mononuclear leukocytes were separated from peripheral blood in 14 control and in 21 patients with CHF.The surface expression of TNF-RII by immunofluorescence flow cytometry was increased in relation to the severity of CHF (NYHA class). TNF-RII mRNA level by Northern blot analysis was relatively higher in patients with advanced CHF.To assess the feasibility of shedding TNF-RII in ^ハmononuclear leukocytes, the cells from patients with CHF and control subjects were incubated in the absence and presence of phorbol myristate acetate (PMA). sTNF-RII in the supernatant with PMA was higher in CHF than control (p<.05). Furthermore, shedding of TNF-RII was higher in the supernatant of mononuclear leukocyts of volunteers treated with 10% serum from CHF than those from control (p<.05). In conclusion, TNF-RII on mononuclear leukocytes was up-regulated in patients with CHF.In addition to feasibility of shedding of TNF-RII on mononuclear leukocytes in CHF,serum from patients with CHF enhanced shedding of TNF-RII on the cells. The presence of CHF affects TNF alpha-TNF receptor system which may modify systemic manifestations including alteration of immune system in CHF.
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