Calcitonin gene-related peptide indirectly inhibits IL-7 responses in pre-B cells by induction of IL-6 and TNF-α in bone marrow

Calcitonin gene-related peptide indirectly inhibits IL-7 responses in pre-B cells by induction of IL-6 and TNF-α in bone marrow
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DOI:
10.1016/j.cellimm.2003.11.010
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发表时间:
2003-12-01
影响因子:
4.3
通讯作者:
McGillis, JP
McGillis, JP
中科院分区:
医学4区
文献类型:
--
作者:
Fernandez, S;Knopf, MA;McGillis, JP

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降钙素基因相关肽(CGRP)具有炎症和免疫调节特性。CGRP直接抑制发育中的B细胞中IL-7诱导的增殖,并且还诱导抑制IL-7应答的可溶性因子。我们鉴定了由CGRP诱导的两种细胞因子IL-6和TNF-α,其抑制IL-7前B细胞应答。CGRP对长期骨髓培养物中IL-6和TNF-α mRNA的诱导是短暂的,IL-6或TNF-α抑制IL-7诱导的集落形成60%。当加入CGRP时,集落形成被完全抑制。TNF-α直接抑制B220(+)/IgM(-)细胞中的IL-7应答,而IL-6仅抑制全骨髓的集落形成。这表明IL-6的作用由骨髓中的其他细胞介导。这些结果表明CGRP对IL-7的间接作用部分依赖于IL-6和TNF-α的诱导。(C)2003年爱思唯尔公司All rights reserved.
Calcitonin gene-related peptide (CGRP) has inflammatory and immunoregulatory properties. CGRP directly inhibits IL-7 induced proliferation in developing B cells and also induces soluble factors that inhibit IL-7 responses. We identified 2 cytokines, IL-6 and TNF-alpha, induced by CGRP, that inhibit IL-7 pre-B cell responses. CGRP induction of IL-6 and TNF-alpha mRNA in long-term bone marrow cultures is transient and IL-6 or TNF-alpha inhibit IL-7 induced colony formation by 60%. When added with CGRP, colony formation is completely inhibited. TNF-alpha directly inhibits IL-7 responses in B220(+)/IgM(-) cells whereas IL-6 inhibits only colony formation with whole bone marrow. This suggests that the effect of IL-6 is mediated by other cells in the bone marrow. These results suggest that the indirect effect of CGRP on IL-7 depends in part on induction of IL-6 and TNF-alpha. (C) 2003 Elsevier Inc. All rights reserved.