2013 Fiscal Year Final Research Report
The role of O-GlcNAc modification in aging-related deterioration of Toll-like receptor signaling in macrophages
| Project/Area Number |
24790593
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hygiene
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| Research Institution | Waseda University |
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Principal Investigator |
SHIRATO Ken 早稲田大学, 人間科学学術院, 助手 (60559384)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 老化 / 加齢 / マクロファージ / リポ多糖 / 炎症 / Toll様受容体 / シグナル伝達 / 翻訳 |
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| Research Abstract |
In the present study, to clarify the molecular mechanism of age-related deterioration of macrophage inflammatory responses, lipopolysaccharide (LPS) responsiveness of peritoneal macrophages were compared between 2-month-old and 12-month-old mice. In middle age, the production of pro-inflammatory cytokine in response to LPS was reduced at the protein level but not at the mRNA level. In addition, Toll-like receptor signaling was not affected in middle age. In contrast, the phosphorylation level of eukaryotic initiation factor (eIF)-2alpha was increased in middle age. These results suggest that macrophage inflammatory responses were deteriorated at the post-transcriptional level in middle age, and that the age-related phenomena are associated with the reduction of mRNA translation mediated by increased phosphorylation of eIF-2alpha.
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