title: Resolvin D1 and aspirin-triggered resolvin D1 regulate histamine-stimulated conjunctival goblet cell secretion.
abstract: Resolution of inflammation is an active process mediated by pro-resolution lipid mediators. As resolvin (Rv) D1 is produced in the cornea, pro-resolution mediators could be effective in regulating inflammatory responses to histamine in allergic conjunctivitis. Two key mediators of resolution are the D-series resolvins RvD1 or aspirin-triggered RvD1 (AT-RvD1). We used cultured conjunctival goblet cells to determine whether histamine actions can be terminated during allergic responses. We found cross-talk between two types of G protein-coupled receptors (GPRs), as RvD1 interacts with its receptor GPR32 to block histamine-stimulated H1 receptor increases in intracellular [Ca(2+)] ([Ca(2+)]i) preventing H1 receptor-mediated responses. In human and rat conjunctival goblet cells, RvD1 and AT-RvD1 each block histamine-stimulated secretion by preventing its increase in [Ca(2+)]i and activation of extracellular regulated-protein kinase (ERK)1/2. We suggest that D-series resolvins regulate histamine responses in the eye and offer new treatment approaches for allergic conjunctivitis or other histamine-dependent pathologies.
authors: Department of Ophthalmology, Massachusetts Eye and Ear, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors: D
authors: D
authors: Li
authors: R R
authors: RR
authors: Hodges
authors: J
authors: J
authors: Jiao
authors: R B
authors: RB
authors: Carozza
authors: M A
authors: MA
authors: Shatos
authors: N
authors: N
authors: Chiang
authors: C N
authors: CN
authors: Serhan
authors: D A
authors: DA
authors: Dartt
mesh_terms: D000818:Animals; D001241:Aspirin / Q000378:metabolism; D012634:Bodily Secretions / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D003233:Conjunctivitis, Allergic / Q000188:drug therapy / Q000276:immunology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020397:Goblet Cells / Q000187:drug effects* / Q000276:immunology; D006632:Histamine / Q000276:immunology / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000378:metabolism
chemical_list: C114479:GPR32 protein, human; D006634:Histamine H1 Antagonists; D043562:Receptors, G-Protein-Coupled; D011969:Receptors, Histamine H1; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D006632:Histamine; D048049:Extracellular Signal-Regulated MAP Kinases; D001241:Aspirin