2011 Fiscal Year Final Research Report
TACE mediate the activity of monocyte via TREM1 shedding
| Project/Area Number |
22791402
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Keywords | TACE / shedding / IL-1 |
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| Research Abstract |
Since the results observed in vivo was not able to be reproduced with the results in vitro about shedding of TREM1 in this research, the object gene was changed into IL-1 receptor and analysis was continued along with the planning plan. IL-1 receptor type II(IL-1RII) is a cytokine receptor that belongs to the IL-1 receptor family and acts as a decoy receptor that competitively inhibits the activity of its ligands due to lacking of most part of the cellular domain, therefore, not mediated IL-1 signaling. IL-1RIIis initially synthesized as a membrane-bound protein, which must be cleaved to become a soluble type. However, little is known about the specific enzyme involved in the proteolytic release of IL-1RII. TNF-α converting enzyme(TACE) is involved in the proteolytic release of the ectodomain of diverse cell surface proteins with critical roles in development, immunity, and hematopoiesis. We found that Tace selectively released IL-1RII, but not IL-1R I and IL-1RAcP, and serum IL-1RII levels in Tace deficient mice were significantly lower, both after LPS treatment and in the absence of such a challenge, further corroborating the relevance of Tace as IL-1RII sheddase in vivo. Moreover, after shedding of IL-1RII from cell surface, IL-1 signaling was further augmented in autologous cells due to less remaining of its inhibitory effect, but had a higher inhibitory effect in remote cells. Therefore, we concludes Tace plays a crucial role on IL-1 signaling by regulating the shedding of IL-1RII from cell surface, and may come to involve a therapeutic advance in the treatment of inflammation diseases.
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Research Products
(2 results)
