Activin A regulates the production of mature interleukin-1beta and interleukin-1 receptor antagonist in human monocytic cells.

Activin A regulates the production of mature interleukin-1beta and interleukin-1 receptor antagonist in human monocytic cells.
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Activin A 调节人单核细胞中成熟 IL-1β 和 IL-1 受体拮抗剂的产生。

DOI:
--
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发表时间:
1998
影响因子:
2.3
通讯作者:
Tatsuji Nisihara
Tatsuji Nisihara
中科院分区:
医学4区
文献类型:
--
作者:
M. Ohguchi;K. Yamato;Y. Ishihara;M. Koide;N. Ueda;N. Okahashi;T. Noguchi;M. Kizaki;Y. Ikeda;H. Sugino;Tatsuji Nisihara

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激活素A是转化生长因子-β家族的一员,由多种细胞产生,参与调节生殖内分泌系统、中胚层诱导和红细胞生成。在本研究中,我们发现激活素A抑制了一种强有力的促炎细胞因子IL-1β的产生,并促进了激活的THP-1和U-937人单核细胞产生IL-1受体拮抗剂(IL-1ra),从而降低了IL-1的生物学活性。Northern印迹分析表明,激活素A对IL-1β和IL-1ra的mRNA积累没有影响,表明激活素A在转录后水平调节IL-1β和IL-1ra的产生。众所周知,IL-1β的非活性前体形式(前-IL-1β)转化为活跃的成熟形式(成熟IL-1β),我们通过免疫印迹分析检测了前-IL-1β和成熟IL-1β的表达水平。虽然激活素A抑制激活的U-937细胞产生成熟的IL-1β,但激活素A不改变原-IL-1β的相对蛋白表达,提示激活素A通过阻止原-IL-1β蛋白水解性转化为成熟的IL-1β而抑制IL-1β的产生。综上所述,这些发现表明,激活素A可能通过调节炎症部位成熟的IL-1β和IL-1ra的产生而发挥抗炎细胞因子的作用。
Activin A, a member of the transforming growth factor-beta (TGF-beta) family, is produced by a variety of cells and implicated in the regulation of the reproductive endocrine system, mesoderm induction, and erythropoiesis. In the present study, we showed that activin A inhibited the production of interleukin-1beta (IL-1beta), a potent proinflammatory cytokine, and enhanced the production of IL-1 receptor antagonist (IL-1ra), in activated THP-1 and U-937 human monocytic cells, resulting in the reduction of IL-1 biologic activity. Northern blot analysis revealed that activin A had no effect on mRNA accumulation of IL-1beta and IL-1ra, indicating that activin A regulates IL-1beta and IL-1ra production at a posttranscriptional level. As it is well known that an inactive precursor form of IL-1beta (pro-IL-1beta) is converted to an active mature form (mature IL-1beta), we examined the expression levels of pro-IL-1beta and mature IL-1beta by immunoblot analysis. Although activin A inhibited the production of mature IL-1beta in activated U-937 cells, the relative protein expression of pro-IL-1beta was unaltered by activin A, suggesting that activin A inhibits IL-1beta production by blocking proteolytic conversion of pro-IL-1beta into mature IL-1beta. Taken together, these findings suggest that activin A may function as an anti-inflammatory cytokine by modulating mature IL-1beta and IL-1ra production in inflammatory sites.
DOI: 10.1073/pnas.81.24.7907
发表时间: 1984-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
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通讯作者: DINARELLO, CA
人骨髓基质细胞和单核细胞中激活素 A 产生的调节。
DOI: --
发表时间: 1992
影响因子: 2.6
作者:
Shao,L;FrigonJr,NL;Sehy,DW;Yu,AL;Lofgren,J;Schwall,R;Yu,J
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激活素对体外人红细胞集落形成的增强作用的表征。
DOI: --
发表时间: 1989
期刊: Blood
影响因子: 20.3
作者:
Yu,J;Shao,L;Vaughan,J;Vale,W;Yu,AL
通讯作者: Yu,AL
DOI: 10.1073/pnas.84.17.6020
发表时间: 1987-09-01
影响因子: 11.1
作者:
ASSOIAN, RK;FLEURDELYS, BE;SPORN, MB
通讯作者: SPORN, MB
DOI: 10.1016/s0065-2776(08)60642-2
发表时间: 1989-01-01
影响因子: --
作者:
DINARELLO, CA
通讯作者: DINARELLO, CA