Dataset Information

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.

SUBMITTER: Li D

PROVIDER: S-EPMC3742576 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Resolvin D1 and aspirin-triggered resolvin D1 regulate histamine-stimulated conjunctival goblet cell secretion.

Li D D Hodges R R RR Jiao J J Carozza R B RB Shatos M A MA Chiang N N Serhan C N CN Dartt D A DA

Mucosal immunology 20130306 6

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 cr ...[more]

PMID: 23462912

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Project description:Many goals in tissue engineering rely on modulating cellular localization and polarization of cell signaling, including the inhibition of inflammatory infiltrate, facilitation of inflammatory cell egress, and clearance of apoptotic cells. Omega-3 polyunsaturated fatty acid-derived resolvins are gaining increasing recognition for their essential roles in inhibition of neutrophil invasion into inflamed tissue and promotion of macrophage phagocytosis of cellular debris as well as their egress to the lymphatics. Biomaterial-based release of lipid mediators is a largely under-explored approach that provides a method to manipulate local lipid signaling gradients in vivo and direct the recruitment and/or polarization of anti-inflammatory cell subsets to suppress inflammatory signaling and enhance angiogenesis and tissue regeneration. The goal of this study was to encapsulate Aspirin-Triggered Resolvin D1 (AT-RvD1) into a degradable biomaterial in order to elucidate the effects of sustained, localized delivery in a model of sterile inflammation. Flow cytometric and imaging analysis at both 1 and 3days after injury showed that localized AT-RvD1 delivery was able significantly increase the accumulation of anti-inflammatory monocytes and M2 macrophages while limiting the infiltration of neutrophils. Additionally, cytokine profiling and longitudinal vascular analysis revealed a shift towards a pro-angiogenic profile with increased concentrations of VEGF and SDF-1?, and increased arteriolar diameter and tortuosity. These results demonstrate the ability of locally-delivered AT-RvD1 to increase pro-regenerative immune subpopulations and promote vascular remodeling. STATEMENT OF SIGNIFICANCE:This work is motivated by our efforts to explore the underlying mechanisms of inflammation resolution after injury and to develop biomaterial-based approaches to amplify endogenous mechanisms of resolution and repair. Though specific lipid mediators have been identified that actively promote the resolution of inflammation, biomaterial-based localized delivery of these mediators has been largely unexplored. We loaded Aspirin-Triggered Resolvin D1 into a PLGA scaffold and examined the effects of sustained, localized delivery on the innate immune response. We found that biomaterial delivery of resolvin was able to enhance the accumulation of pro-regenerative populations of immune cells, including anti-inflammatory monocytes, population that has never before been shown to respond to resolvin treatment, and also enhance vascular remodeling in response to tissue injury.

Dataset Information

Resolvin D1 and aspirin-triggered resolvin D1 regulate histamine-stimulated conjunctival goblet cell secretion.

Publications

Resolvin D1 and aspirin-triggered resolvin D1 regulate histamine-stimulated conjunctival goblet cell secretion.

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