Conjunctival goblet cell secretion stimulated by leukotrienes is reduced by resolvins D1 and E1 to promote resolution of inflammation.
Conjunctival goblet cell secretion stimulated by leukotrienes is reduced by resolvins D1 and E1 to promote resolution of inflammation.
复制标题
DOI：
10.4049/jimmunol.1000833
复制
发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
Serhan CN
中科院分区：
文献类型：
--
作者：
Dartt DA;Hodges RR;Li D;Shatos MA;Lashkari K;Serhan CN
结膜是一种覆盖巩膜并衬在眼睑内侧的粘膜。整个结膜都是杯状细胞，分泌粘蛋白来保护眼睛。慢性炎性疾病如过敏性结膜炎和早期干眼症导致杯状细胞粘蛋白分泌到泪液中增加和眼表疾病。本研究的目的是确定炎症介质的作用，白三烯和proresolution resolvins，从培养的大鼠和人结膜杯状细胞分泌。我们发现，两个半胱氨酰白三烯（CysLT）受体，CysLT 1和CysLT 2，存在于大鼠结膜和大鼠和人类培养的结膜杯状细胞。所有白三烯LTB 4、LTC 4、LTD 4和LTE 4以及PGD 2均刺激大鼠杯状细胞中的杯状细胞分泌。LTD 4和LTE 4增加细胞内Ca ~（2+）浓度（[Ca ~（2+）]i），LTD 4激活ERK 1/2。CysLT 1受体拮抗剂MK 571可显著降低LTD 4刺激的大鼠杯状细胞分泌和[Ca 2 +]i的升高。在培养的大鼠杯状细胞中，Resolvins D1（RvD 1）和E1（RvE 1）完全减少LTD 4刺激的杯状细胞分泌。LTD 4诱导的人杯状细胞分泌被RvD 1阻断。RvD 1和RvE 1阻止LTD 4和LTE 4刺激的[Ca 2 +]i增加，以及LTD 4激活ERK 1/2。我们的结论是，半胱氨酰白三烯刺激结膜杯状细胞粘液分泌LTD 4使用CysLT 1受体。通过阻止[Ca 2 +]i的增加以及RvD 1和RvE 1对ERK 1/2的激活来终止刺激的分泌。
The conjunctiva is a mucous membrane that covers the sclera and lines the inside of the eyelids. Throughout the conjunctiva are goblet cells that secrete mucins to protect the eye. Chronic inflammatory diseases such as allergic conjunctivitis and early dry eye lead to increased goblet cell mucin secretion into tears and ocular surface disease. The purpose of this study was to determine the actions of the inflammatory mediators, the leukotrienes and the proresolution resolvins, on secretion from cultured rat and human conjunctival goblet cells. We found that both cysteinyl leukotriene (CysLT) receptors, CysLT1 and CysLT2, were present in rat conjunctiva and in rat and human cultured conjunctival goblet cells. All leukotrienes LTB4, LTC4, LTD4, and LTE4, as well as PGD2, stimulated goblet cell secretion in rat goblet cells. LTD4 and LTE4 increased the intracellular Ca2+ concentration ([Ca2+]i), and LTD4 activated ERK1/2. The CysLT1 receptor antagonist MK571 significantly decreased LTD4-stimulated rat goblet cell secretion and the increase in [Ca2+]i. Resolvins D1 (RvD1) and E1 (RvE1) completely reduced LTD4-stimulated goblet cell secretion in cultured rat goblet cells. LTD4-induced secretion from human goblet cells was blocked by RvD1. RvD1 and RvE1 prevented LTD4- and LTE4-stimulated increases in [Ca2+]i, as well as LTD4 activation of ERK1/2. We conclude that cysteinyl leukotrienes stimulate conjunctival goblet cell mucous secretion with LTD4 using the CysLT1 receptor. Stimulated secretion is terminated by preventing the increase in [Ca2+]i and activation of ERK1/2 by RvD1 and RvE1.
登录
查看更多内容
影响因子：
30.5
作者：
Haworth, Oliver;Cernadas, Manuela;Levy, Bruce D.
通讯作者：
Levy, Bruce D.
影响因子：
4.2
作者：
Nieto, N;Torres, MI;Gil, A
通讯作者：
Gil, A
影响因子：
--
作者：
Kim, DH;Chu, HS;Lee, HM
通讯作者：
Lee, HM
影响因子：
2.9
作者：
Gersemann, Michael;Becker, Svetlana;Stange, Eduard Friedrich
通讯作者：
Stange, Eduard Friedrich
影响因子：
4.8
作者：
Hasturk, H.;Kantarci, A.;Van Dyke, T. E.
通讯作者：
Van Dyke, T. E.