Transforming growth factor 13 is the prototype of a large family of secreted factors that regulate multiple biological processes. In the immune system, TGF beta acts as an anti-inflammatory and immunosuppressive molecule, whereas the cytokine interleukin (IL)-1 beta is a crucial mediator of inflammatory responses and induces proinflammatory genes and acute phase proteins. Here, we present evidence for the existence of a direct inhibitory interaction between the IL-1 beta and TGF beta signaling cascades that is not dependent on IL-1 beta-induced SMAD7 expression. IL-1 beta and its downstream mediator TAK1 inhibit SMAD3-mediated TGF beta target gene activation, whereas SMAD3 nuclear translocation and DNA binding in response to TGF beta are not affected. IL-1 beta transiently induces association between TAK1 and the MAD homology 2 domain of SMAD3, resulting in SMAD3 phosphorylation. Furthermore, IL-1 beta alleviates the inhibitory effect of TGF beta on in vitro hematopoietic myeloid colony formation. In conclusion, our data provide evidence for the existence of a direct inhibitory effect of the IL-1 beta-TAK1 pathway on SMAD3-mediated TGF beta signaling, resulting in reduced TGF beta target gene activation and restored proliferation of hematopoietic progenitors.
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Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan
Kurokawa, M
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Mitani, K
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Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan
Mitani, K
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Imai, Y
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Ogawa, S
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Yazaki, Y
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Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan
Yazaki, Y
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Hirai, H
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Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan
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Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan
Kurokawa, M
;
Mitani, K
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan
Mitani, K
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论文数: 引用数:
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机构:
Imai, Y
;
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机构:
Ogawa, S
;
Yazaki, Y
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan
Yazaki, Y
;
Hirai, H
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan