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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 [Ca 2+ ] ([Ca 2+ ] i ) and on histamine-stimulated responses. LXA 4  increased mucin secretion and [Ca 2+ ] 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, [Ca 2+ ] i , and ERK1/2 activation through activation of β-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.

Lipoxin A4 Counter-regulates Histamine-stimulated Glycoconjugate Secretion in Conjunctival Goblet Cells