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

Conjunctival goblet cells synthesize and secrete mucins which play an important role in protecting the ocular surface. Pro-resolution mediators, such as lipoxin A₄ (LXA₄), 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 LXA₄ on cultured human conjunctival goblet cell mucin secretion and increase in intracellular [Ca²⁺] ([Ca²⁺]_i) and on histamine-stimulated responses. LXA₄ increased mucin secretion and [Ca²⁺]_i, and activated ERK1/2 in human goblet cells. Addition of LXA₄ before resolvin D1 (RvD1) decreased RvD1 responses though RvD1 did not block LXA₄ responses. LXA₄ inhibited histamine-stimulated increases in mucin secretion, [Ca²⁺]_i, and ERK1/2 activation through activation of β-adrenergic receptor kinase 1. We conclude that conjunctival goblet cells respond to LXA₄ 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.