Maresin 1, a specialized proresolving mediator, stimulates intracellular [Ca2+] and secretion in conjunctival goblet cells

Mucin secretion from conjunctival goblet cells forms the tear film mucin layer and requires regulation to function properly. Maresin 1 (MaR1) is a specialized proresolving mediator produced during the resolution of inflammation. We determined if MaR1 stimulates mucin secretion and signaling pathways used. Cultured rat conjunctival goblet cells were used to measure the increase in intracellular Ca2+ ([Ca-2(+)](i)) concentration and mucin secretion. MaR1-increased [Ca2+](i) and secretion were blocked by inhibitors of phospholipase C, protein kinase C, Ca2+/calmodulin-dependent protein kinase II, and extracellular-regulated kinase 1/2. MaR1 added before addition of histamine counterregulated histamine-stimulated increase in [Ca2+](i) and secretion. We conclude that MaR1 likely has two actions in conjunctival goblet cells: first, maintaining optimal tear film mucin levels by increasing [Ca2+](i) and stimulating mucin secretion in health and, second, attenuating the increase in [Ca2+](i) and overproduction of mucin secretion by counterregulating the effect of histamine as occurs in ocular allergy.