Resolvin E1 Reduces Leukotriene B4-Induced Intracellular Calcium Increase and Mucin Secretion in Rat Conjunctival Goblet Cells

Leukotriene B4 (LTB4) is a major proinflammatory mediator important in host defense, whereas resolvins (Rvs) are produced during the resolution phase of inflammation. The authors determined the actions of both RvE1 and RvD1 on LTB4-induced responses of goblet cells cultured from rat conjunctiva. The responses measured were an increase in the intracellular [Ca2+] ([Ca-2(+)](i)) and high- molecular-weight glycoprotein secretion. Treatment with RvE1 or RvD1 for 30 minutes significantly blocked the LTB4-induced [Ca-2(+)](i) increase. The actions of RvE1 on LTB4-induced [Ca-2(+)](i) increase were reversed by siRNA for the RvE1 receptor, and the actions of RvD1 were reversed by an RvD1 receptor inhibitor. The RvE1 and RvD1 block of LTB4-stimulated increase in [Ca-2(+)](i) was also reversed by an inhibitory peptide to beta-adrenergic receptor kinase. LTB4 and block of the LTB4-stimulated increase in [Ca-2(+)](i) by RvE1 and RvD1 were partially mediated by the depletion of intracellular Ca2+ stores. RvE1, but not RvD1, counterregulated the LTB4-induced high-molecular-weight glycoprotein secretion. Thus, both RvE1 and RvD1 receptors directly inhibit LTB4 by phosphorylating the LTB4 receptor using beta adrenergic receptor kinase. RvE1 receptor counterregulates the LTB4-induced increase in [Ca-2(+)](i) and secretion, whereas RvD1 receptor only counterregulates LTB4-induced [Ca-2(+)](i) increase.