1995 Fiscal Year Final Research Report Summary
Apoptosis of macrophages and T cells in periodontal tissues : Its molecular mechanisms and biological roles
| Project/Area Number |
06454528
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional basic dentistry
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| Research Institution | TOKYO DENTAL COLLEGE |
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Principal Investigator |
KIZAKI Harutoshi Tokyo Dental College, Professor, 歯学部, 教授 (60051653)
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| Co-Investigator(Kenkyū-buntansha) |
TANIMOTO Yutaka Tokyo Dental College, Instructor, 歯学部, 助手 (10276975)
ONISHI Yoshiaki Tokyo Dental College, Instructor, 歯学部, 助手 (60233219)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Periodontitis / Apoptosis / Monocytes / Macrophages / T cells / Thymocytes / Tyrosine phosphorylation / LPS |
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| Research Abstract |
Apoptosis is a physiological cell death process of eliminating unwanted cells from living organisms during embryogenic and adult development. It also function in regulation of survival of inflammatory cells in chronic inflammatory lesions. The aims of the present study are to elucidate the molecular mechanisms and roles of apoptosis of monocytes, macrophages and T cells which play important roles in periodontitis. Thymocyte apoptosis is found to be regulated by at least two steps of protein phosphorylation ; one is triggering apoptosis, another is involved in progressing apoptosis. The latter protein phosphorylation occurs at a later stage of the process and seems to be common to the apoptosis induced by various stimuli. Thymocyte apoptosis induced by various stimuli was inhibited by inhibitors of proteasome, suggesting an important role of proteases in apoptosis. Apoptosis induced by dexamethasone in spleen T cells was paritially inhibited by cycloheximide, though cycloheximide itself
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induced apoptosis. Thus, there exist two mechanisms of apoptosis in mature T cells, protein synthesis-dependent and-independent. Spleen T cells were resistant to TPA or A23187 which was able to induce apoptosis in thymocytes. However, T cells bacame relatively sensitive to A23187 after cultivation for 3 days in the presence of IL-2, suggesting that activation-induced cell death is induced in part by calcium-mediated signaling. IL-2-dependent CTLL-2 cells underwent apoptosis when IL-2 was withdrawn accompanying by decreased in protein tyrosine phosphorylation in nuclear protein. Depletion of IL-2 is a cause of activation-induced cell death which participates in resolution of inflammation. Further studies on the molecular mechanisms of apoptosis in thymocytes and T cells are required. Monocyte and macroophage cell lines, U937 and P388D1 cells underwent apoptosis when serum was depleted. The apoptosis was inhibited by TNF-alpha or substance P accompanying by increased protein tyrosine phosphorylation. The results suggest cytokines or neuropeptides modualate inflammatory responses through regulating survival of inflammatory cells. Less
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