Interleukin-6 signaling and embryonic mouse submandibular salivary gland morphogenesis.
Interleukin-6 signaling and embryonic mouse submandibular salivary gland morphogenesis.
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Interleukin-6 信号传导和胚胎小鼠颌下唾液腺形态发生。
DOI：
10.1159/000047840
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Jaskoll,T
中科院分区：
文献类型：
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作者：
Melnick,M;Chen,H;Zhou,YM;Jaskoll,T
白介素 6 (IL-6) 是一种多功能细胞因子，可介导细胞生长、分化和存活。本研究的目的是研究 IL-6 信号在胚胎小鼠颌下唾液腺 (SMG) 形态发生中的可能功能。在表征了该通路各个成分的体内 mRNA 和蛋白表达后，我们利用体外策略来研究增强的 IL-6 诱导信号传导和 IL-6 与同源受体结合的免疫扰动的表型结果。这些实验表明：(1) 随着 SMG 发育的进行，IL-6 mRNA 显着增加，这与 TNF 转录物水平高度相关；(2) IL-6 及其同源受体免疫定位于从小管阶段到晚期终芽阶段的 SMG 分支上皮中，IL-6 途径的其他成分也是如此；(3) 与对照相比，补充 IL-6 的外植体的总体大小和数量显着增加(4)在抗IL-6中和抗体存在下培养的SMG外植体，上皮导管和终芽显着减少，同时上皮细胞增殖显着增加；(4)上皮导管和终芽显着减少，同时细胞增殖显着下降，细胞凋亡显着增加。综上所述，我们的实验结果表明 IL-6 信号传导对于 SMG 发育稳态很重要。
Interleukin-6 (IL-6) is a multifunctional cytokine that mediates cell growth, differentiation, and survival. It was the objective of the present study to investigate the possible function (s) of IL-6 signaling in embryonic mouse submandibular salivary gland (SMG) morphogenesis. After characterizing in vivo mRNA and protein expression of various constituents of this pathway, we utilized in vitro strategies to investigate the phenotypic outcomes of enhanced IL-6-induced signaling and immunoperturbation of IL-6 binding to cognate receptors. These experiments demonstrate:(1) there is a significant increase of IL-6 mRNA with progressive SMG development, and that this is highly correlated with TNF transcript levels;(2) IL-6 and its cognate receptors are immunolocalized in SMG branching epithelia from the canalicular stage to the late terminal bud stage, as are other constituents of the IL-6 pathway;(3) as compared to controls, IL-6-supplemented explants exhibit a substantial increase in overall size and in the number of ductal branches and terminal buds, as well as a highly significant increase in epithelial cell proliferation;(4) SMG explants cultured in the presence of anti-IL-6 neutralizing antibodies exhibit a marked decrease in epithelial ducts and terminal buds, concomitant with a significant decline in cell proliferation and a highly significant increase in apoptosis. Taken together, our experimental results indicate that IL-6 signaling is important to SMG developmental homeostasis.