Lipoxin A4 Counter-regulates Histamine-stimulated Glycoconjugate Secretion in Conjunctival Goblet Cells
Lipoxin A4 Counter-regulates Histamine-stimulated Glycoconjugate Secretion in Conjunctival Goblet Cells
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DOI：
10.1038/srep36124
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发表时间：
2016-11-08
影响因子：
4.6
通讯作者：
Dartt, Darlene A.
中科院分区：
文献类型：
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作者：
Hodges, Robin R.;Li, Dayu;Dartt, Darlene A.
结膜杯状细胞合成和分泌粘蛋白，在保护眼表中起重要作用。促消退介质，如脂氧素A（4）（LXA（4）），在炎症使组织恢复稳态期间产生，并且也在非炎症组织中产生。本研究的目的是确定LXA（4）对培养的人结膜杯状细胞粘蛋白分泌和细胞内[Ca 2 +]（[Ca 2 +]（i））增加以及组胺刺激反应的作用。LXA（4）增加人杯状细胞粘蛋白分泌和[Ca ~（2+）]（i），并激活ERK 1/2。在消退素D1（RvD 1）之前加入LXA（4）可降低RvD 1的反应，尽管RvD 1并不阻断LXA（4）的反应。LXA（4）通过激活β-肾上腺素能受体激酶1抑制组胺刺激的粘蛋白分泌、[Ca 2 +]（i）和ERK 1/2激活的增加。我们的结论是，结膜杯状细胞通过ALX/FPR 2受体对LXA（4）产生反应，以维持眼表的稳态并调节组胺反应，这可能为过敏性结膜炎和干眼病提供新的治疗方法。
Conjunctival goblet cells synthesize and secrete mucins which play an important role in protecting the ocular surface. Pro-resolution mediators, such as lipoxin A(4) (LXA(4)), are produced during inflammation returning the tissue to homeostasis and are also produced in non-inflamed tissues. The purpose of this study was to determine the actions of LXA(4) on cultured human conjunctival goblet cell mucin secretion and increase in intracellular [Ca2+] ([Ca2+](i)) and on histamine-stimulated responses. LXA(4) increased mucin secretion and [Ca2+](i), and activated ERK1/2 in human goblet cells. Addition of LXA(4) before resolvin D1 (RvD1) decreased RvD1 responses though RvD1 did not block LXA(4) responses. LXA(4) inhibited histamine-stimulated increases in mucin secretion, [Ca2+](i), and ERK1/2 activation through activation of beta-adrenergic receptor kinase 1. We conclude that conjunctival goblet cells respond to LXA(4) through the ALX/FPR2 receptor to maintain homeostasis of the ocular surface and regulate histamine responses and could provide a new therapeutic approach for allergic conjunctivitis and dry eye diseases.