Interaction of IFN-γ with cholinergic agonists to modulate rat and human goblet cell function.
Interaction of IFN-γ with cholinergic agonists to modulate rat and human goblet cell function.
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DOI：
10.1038/mi.2015.53
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发表时间：
2016-01
影响因子：
8
通讯作者：
Dartt DA
中科院分区：
文献类型：
--
作者：
García-Posadas L;Hodges RR;Li D;Shatos MA;Storr-Paulsen T;Diebold Y;Dartt DA
杯状细胞分布在湿表面粘膜，包括眼结膜、肠和鼻等。这些细胞通过分泌与包括病原体、过敏原和颗粒污染物的环境成分相互作用的高分子量粘蛋白而作为先天免疫系统的一部分发挥作用。在此，我们确定了IFN-γ（一种Th 1细胞因子）在干眼中的增加是否改变了杯状细胞的功能。培养大鼠和人结膜杯状细胞。在用IFN-γ刺激后，在有或没有胆碱能激动剂卡巴胆碱的情况下，测量细胞内[Ca 2 +]（[Ca 2 +]i）、高分子量糖缀合物分泌和增殖的变化。IFN-γ本身增加大鼠和人杯状细胞中的[Ca 2 +]i，并阻止卡巴胆碱引起的[Ca 2 +]i增加。卡巴胆碱阻止IFN-γ介导的[Ca 2 +]i增加。IFN-γ和毒蕈碱受体之间的这种串扰可能部分是由于使用相同的Ca 2 +i库，但也来自接近[Ca 2 +]i增加的信号传导途径的相互作用。IFN-γ阻断卡巴胆碱诱导的高分子量糖缀合物分泌并减少杯状细胞增殖。我们的结论是，干眼病中IFN-γ水平的增加可以解释这种病理中典型的杯状细胞缺乏和粘蛋白缺乏。IFN-γ在呼吸道和胃肠道中也具有类似的功能。
Goblet cells populate wet-surfaced mucosa including the conjunctiva of the eye, intestine, and nose, among others. These cells function as part of the innate immune system by secreting high molecular weight mucins that interact with environmental constituents including pathogens, allergens, and particulate pollutants. Herein we determined whether IFN-γ, a Th1 cytokine increased in dry eye, alters goblet cell function. Goblet cells from rat and human conjunctiva were cultured. Changes in intracellular [Ca2+] ([Ca2+]i), high molecular weight glycoconjugate secretion, and proliferation were measured after stimulation with IFN-γ with or without the cholinergic agonist carbachol. IFN-γ itself increased [Ca2+]i in rat and human goblet cells and prevented the increase in [Ca2+]i caused by carbachol. Carbachol prevented IFN-γ-mediated increase in [Ca2+]i. This cross-talk between IFN-γ and muscarinic receptors may be partially due to use of the same Ca2+i reservoirs, but also from interaction of signaling pathways proximal to the increase in [Ca2+]i. IFN-γ blocked carbachol-induced high molecular weight glycoconjugate secretion and reduced goblet cell proliferation. We conclude that increased levels of IFN-γ in dry eye disease could explain the lack of goblet cells and mucin deficiency typically found in this pathology. IFN-γ could also function similarly in respiratory and gastrointestinal tracts.