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

Resolvin E1 Reduces Leukotriene B4-Induced Intracellular Calcium Increase and Mucin Secretion in Rat Conjunctival Goblet Cells.
Am J Pathol. 2020 Jun 16;:
Authors: Yang M, Bair JA, Hodges RR, Serhan CN, Dartt DA
Abstract
Leukotriene B4 (LTB4) is a major proinflammatory mediator important in host defense whereas resolvins (Rvs) are produced during the resolution phase of inflammation. We 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+] ([Ca2+]i) and high molecular weight glycoprotein secretion. Treatment with RvE1 or RvD1 for 30 min significantly blocked the LTB4-induced [Ca2+]i increase. The actions of RvE1 on LTB4-induced [Ca2+]i increase were reversed by siRNA for the RvE1 receptor and of RvD1 were reversed by an inhibitor to the RvD1 receptor. The RvE1 and RvD1 block of LTB4-stimulated increase in [Ca2+]i was also reversed by an inhibitory peptide to β-adrenergic receptor kinase (BARK1). LTB4- and block of the LTB4-stimulated increase in [Ca2+]i by RvE1 and RvD1 were partially mediated by the depletion of intracellular Ca2+ stores. RvE1, but not RvD1, counter-regulated the LTB4-induced high molecular weight glycoprotein secretion. Thus, both RvE1 and RvD1 receptors directly inhibit LTB4 by phosphorylating the LTB4 receptor (BLT1) using BARK1. RvE1 receptor counter-regulates the LTB4-induced incr...

Source: The American Journal of Pathology - June 15, 2020 Category: Pathology Authors: Yang M, Bair JA, Hodges RR, Serhan CN, Dartt DA Tags: Am J Pathol Source Type: research