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 [Ca(2+)] ([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 β-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 Ca(2+) 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 β 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.