Bradykinin inhibition of EGF- and PDGF-induced DNA synthesis in human fibroblasts.
Bradykinin inhibition of EGF- and PDGF-induced DNA synthesis in human fibroblasts.
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缓激肽抑制 EGF 和 PDGF 诱导的人成纤维细胞 DNA 合成。
DOI：
10.1152/ajpcell.1993.265.2.c477
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Olson,MS
中科院分区：
文献类型：
--
作者：
McAllister,BS;Leeb-Lundberg,F;Olson,MS
缓激肽在几种类型的细胞中表现出增殖的影响，然而，在本研究中，缓激肽没有促进DNA合成，但实际上抑制了人牙龈成纤维细胞（HGF）中表皮生长因子（EGF）和血小板衍生生长因子（PDGF）诱导的DNA合成。这种剂量依赖性抑制作用是一种特异性的细胞内相互作用，因为当加入100 nM时，EGF浓度的增加并不抵消缓激肽的抑制作用。磷酸肌醇-钙信号级联反应是缓激肽的抑制作用的一个可能的相互作用点;然而，缓激肽和EGF之间没有观察到磷酸肌醇或细胞内钙通量的产生的相互作用。缓激肽的抑制作用似乎不是EGF受体的反调节的结果，因为EGF介导的自磷酸化没有受到缓激肽的负面影响。缓激肽刺激的前列腺素E2（PGE 2）释放增强EGF，并在吲哚美辛的存在下，缓激肽的EGF诱导的DNA合成的抑制被最小化。结果表明，缓激肽可以抑制EGF和PDGF诱导的DNA合成，并建议PGE 2的合成是负责观察缓激肽抑制EGF诱导的DNA合成。
Bradykinin exhibits proliferative influences in several types of cells; however, in the present study, bradykinin did not promote DNA synthesis but actually inhibited the DNA synthesis induced by epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) in human gingival fibroblasts (HGF). This dose-dependent inhibitory effect was a specific intracellular interaction in that increasing concentrations of EGF did not counteract the inhibitory actions of bradykinin when added at 100 nM. The phosphoinositide-calcium signaling cascade is a likely point of interaction for the inhibitory influences of bradykinin; however, no interactions between bradykinin and EGF were observed with the generation of inositol phosphates or intracellular calcium fluxes. The inhibitory influences of bradykinin do not appear to be the result of a transmodulation of the EGF receptor, since EGF-mediated autophosphorylation was not negatively affected by bradykinin. Bradykinin-stimulated prostaglandin E2 (PGE2) release was potentiated by EGF, and, in the presence of indomethacin, the inhibition of the EGF-induced DNA synthesis by bradykinin was minimized. The results presented demonstrate that bradykinin can inhibit EGF- and PDGF-induced DNA synthesis and suggest that PGE2 synthesis is responsible for the observed bradykinin inhibition of EGF-induced DNA synthesis.