Modulation of Conjunctival Goblet Cell Function by Inflammatory Cytokines

Modulation of Conjunctival Goblet Cell Function by Inflammatory Cytokines
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DOI:
10.1155/2013/636812
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发表时间:
2013-01-01
影响因子:
4.6
通讯作者:
Masli, S.
Masli, S.
中科院分区:
医学3区
文献类型:
--
作者:
Contreras-Ruiz, L.;Ghosh-Mitra, A.;Masli, S.

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干燥综合征相关的眼表炎症的特征是分泌功能的丧失和分泌粘蛋白的杯状细胞数量的改变。这种变化是眼表炎症性疾病的显著特征,可归因于炎症;然而,炎性细胞因子对结膜杯状细胞功能的确切影响在很大程度上仍然未知。在这项研究中,我们建立了小鼠结膜组织杯状细胞的原代培养,并评估了在干燥综合征小鼠模型(血小板反应蛋白-1缺陷小鼠)结膜中检测到的炎症细胞因子对其功能的影响。我们发现,tnf - α主要诱导杯状细胞凋亡。和IFN-gamma。这两种细胞因子还能抑制胆碱能刺激下杯状细胞分泌粘蛋白,而IL-6则能增强这种分泌。在IL-13或IL-17存在的情况下,未检测到分泌反应的变化。杯状细胞对所有细胞因子均有不同程度的增殖反应,其中对IL-13的反应最大,其次是IL-6。因此,我们的研究结果表明,在眼表疾病期间结膜中表达的炎症细胞因子直接破坏了结膜杯状细胞的功能,损害了泪液的保护功能,从而导致眼表损伤。
Ocular surface inflammation associated with Sjogren's syndrome is characterized by a loss of secretory function and alteration in numbers of mucin secreting goblet cells. Such changes are a prominent feature of ocular surface inflammatory diseases and are attributed to inflammation; however, the exact effect of the inflammatory cytokines on conjunctival goblet cell function remains largely unknown. In this study, we developed a primary culture of mouse goblet cells from conjunctival tissue and evaluated the effects on their function by inflammatory cytokines detected in the conjunctiva of mouse model of Sjogren's syndrome (Thrombospondin-1 deficient mice). We found that apoptosis of goblet cells was primarily induced by TNF-alpha. and IFN-gamma. These two cytokines also inhibited mucin secretion by goblet cells in response to cholinergic stimulation, whereas IL-6 enhanced such secretion. No changes in secretory response were detected in the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in response to all the tested cytokines with the greatest response to IL-13 followed by IL-6. Our results therefore reveal that inflammatory cytokines expressed in the conjunctiva during an ocular surface disease directly disrupt conjunctival goblet cell functions, compromising the protective function of tears, thereby contributing to ocular surface damage.