INTERLEUKIN-1 - A MITOGEN FOR HUMAN VASCULAR SMOOTH-MUSCLE CELLS THAT INDUCES THE RELEASE OF GROWTH-INHIBITORY PROSTANOIDS
INTERLEUKIN-1 - A MITOGEN FOR HUMAN VASCULAR SMOOTH-MUSCLE CELLS THAT INDUCES THE RELEASE OF GROWTH-INHIBITORY PROSTANOIDS
复制标题
DOI：
10.1172/jci113346
复制
发表时间：
1988-02-01
影响因子：
15.9
通讯作者：
FRIEDMAN, GB
中科院分区：
文献类型：
--
作者：
LIBBY, P;WARNER, SJC;FRIEDMAN, GB
人们对定义在以单核吞噬细胞的存在为特征的各种状态下启动细胞异常增殖的信号非常感兴趣。由于 IL-1 是活化的人单核细胞的主要分泌产物，我们检查了这种细胞因子是否可以刺激人血管平滑肌细胞 (SMC) 的生长。重组IL-1 (rIL-1).alpha 均不存在。 （≤ 5.0 ng/ml）也不是 .beta。 (≤100 ng/ml) 在通常条件下的 2 天孵育期间刺激 sMC 生长。 IL-1确实刺激SMC产生前列腺素类化合物，例如PGE1或PGE2，可以抑制SMC增殖。当前列腺素合成被吲哚美辛或阿司匹林抑制时，rIL-1.α。和.beta。 (≥1 ng/ml) 显着增加 SMC 生长。在长期实验（7-28 天）中，即使在没有环氧合酶抑制剂的情况下，rIL-1 也会刺激 SMC 的生长。向吲哚美辛处理的 SMC 中添加外源性 PGE1 或 PGE2（但不包括 PGF1.α、PGF2.α、PGI2）可阻断其对 rIL-1 的促有丝分裂反应。 IL-1 抗体（但不是血小板衍生生长因子 [PDGF]）抗体消除了 SMC 对 rIL-1 的有丝分裂反应。通过 Northern 分析确定，将 SMC 暴露于 rIL-1 或 PDGF 会导致 c-fos 原癌基因快速（1 小时时最大）和瞬时（3 小时基线）表达。我们得出结论，IL-1 是人类 SMC 的有效有丝分裂原。 IL-1 同时诱导的内源性前列腺素生成似乎会在短期（2 天）内拮抗这种生长促进作用，但在更长时间的暴露期间不会拮抗这种作用。因此，组织炎症或损伤部位激活的单核细胞产生的 IL-1 可能对 SMC 增殖产生积极和消极的影响，这些影响在时间上是不同的。
There is much interest in defining the signals that initiate abnormal proliferation of cells in a variety of states characterized by the presence fo mononuclear phagocytes. Since IL-1 is a major secretory product of activated human monocytes we examined whether this cytokine can stimulate the growth of human vascular smooth muscle cells (SMC). Neither recombinant IL-1 (rIL-1) .alpha. (.ltoreq. 5.0 ng/ml) nor .beta. (.ltoreq. 100 ng/ml) stimulated sMC growth during 2-d incubations under usual conditions. IL-1 did stimulate SMC to produce prostanoids such as PGE1 or PGE2 that can inhibit SMC proliferation. When prostaglandin synthesis was inhibited by indomethacin or aspirin both rIL-1 .alpha. and .beta. (.gtoreq. 1 ng/ml) markedly increased SMC growth. In longer-term experiments (7-28 d) rIL-1 stimulated the growth of SMC even in the absence of cyclooxygenase inhibitors. The addition of exogenous PGE1 or PGE2 (but not PGF1.alpha., PGF2.alpha., PGI2) to indomethacin-treated SMC blocked their mitogenic response to rIL-1. Antibody to IL-1 (but not to platelet-derived growth factor [PDGF]) abolished the mitogenic response of SMC to rIL-1. Exposure of SMC to rIL-1 or PDGF caused rapid (maximal at 1 h) and transient (baseline by 3 h) expresssion of the c-fos proto-oncogene, determined by Northern analysis. We conclude that IL-1 is a potent mitogen for human SMC. Endogenous prostanoid production simultaneously induced by IL-1 appears to antagonize this growth-promoting effect in the short term (2 d) but not during more prolonged exposures. IL-1 produced by activated monocytes at sites of tissue inflammation or injury may thus mediate both positive and negative effects on SMC proliferation that are temporally distinct.