2002 Fiscal Year Final Research Report Summary
Biological activity of limitin and adiponectin
| Project/Area Number |
13671064
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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 |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
ORITANI Kenji Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70324762)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Hitoshi Osaka University, Hospital, Medical Staff, 医学部附属病院, 医員(臨床研究)
TOMIYAMA Yoshiaki Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80252667)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Adiponectin / fat cell / Limitin / interferon / signal / myelosuppression |
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| Research Abstract |
(1) Adiponectin: Adiponectin, one of the major products of adipocytes, strongly inhibited B lymphopoiesis in long-term bane marrow cultures, but only when stromal cells were present. Cox-2 inhibitors abrogated the response of early lymphoid progenitors to adiponectin in stromal cell containing cultures. Furthermore, prostaglandin E2, a major product of Cox-2 activity; had a direct inhibitory influence on purified hematopoietic cells, suggesting a possible mechanism of adiponectin action in culture.
(2) Limitin: Limitin, an IFN-like cytokine, augmented the killer activity of cytotoxic T lymphocytes as well as the surface expression of MHC class I molecules. Limitin inhibited the proliferation of FDCP-1 cells stably transfected with p210bcr/abl. Limitin also induced antiviral state against EMCV, MHV, and HSV. Although the above functions of limitin were similar to those of IFN-α, higher concentration of limitin was required than IFN-α for the inhibition of CFU-IL7 or CFU-Meg colony formation. Limitin could not inhibit CFU-GM or BFU-E colony formation while IFN-α did. These data suggest that limitin may be less toxic than other IFNs, and therefore may have a unique clinical niche for treatment of diseases where type I IFNs have proven useful. In signals for IFN-mediated myelosuppression, the disruption of Tyk2 completely abrogated IFN-α-induced inhibition of CFU-IL7 and CFU-Meg colony formation. We are now analyzing the difference of downstream signals of Tyk2 between limitin and IFN-α.
Immunohistochemical analysis revealed that the limitin protein is constitutively produced by mature T lymphocytes in spleen and thymus. Unlikely other IFNs, limitin expression was not up-regulated by virus-infection. These data may suggest that limitin acts to avoid virus-infection or to eliminate harmful cells in healthy conditions.
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Research Products
(12 results)
