Anti-Inflammatory and Pro-Resolving Actions of the N-Terminal Peptides Ac2-26, Ac2-12, and Ac9-25 of Annexin A1 on Conjunctival Goblet Cell Function.

Autor: Lyngstadaas AV; Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway., Olsen MV; Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway., Bair J; Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts., Yang M; Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts., Hodges RR; Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts., Utheim TP; Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway; Department of Plastic and Reconstructive Surgery, University of Oslo, Oslo, Norway., Serhan CN; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Dartt DA; Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Department of Plastic and Reconstructive Surgery, University of Oslo, Oslo, Norway. Electronic address: darlene_dartt@meei.harvard.edu.
Jazyk: angličtina
Zdroj: The American journal of pathology [Am J Pathol] 2023 Nov; Vol. 193 (11), pp. 1817-1832. Date of Electronic Publication: 2023 Jul 07.
DOI: 10.1016/j.ajpath.2023.05.020
Abstrakt: Annexin A1 (AnxA1) is the primary mediator of the anti-inflammatory actions of glucocorticoids. AnxA1 functions as a pro-resolving mediator in cultured rat conjunctival goblet cells to ensure tissue homeostasis through stimulation of intracellular [Ca 2+ ] ([Ca 2+ ] i ) and mucin secretion. AnxA1 has several N-terminal peptides with anti-inflammatory properties of their own, including Ac2-26, Ac2-12, and Ac9-25. The increase in [Ca 2+ ] i caused by AnxA1 and its N-terminal peptides in goblet cells was measured to determine the formyl peptide receptors used by the compounds and the action of the peptides on histamine stimulation. Changes in [Ca 2+ ] i were determined by using a fluorescent Ca 2+ indicator. AnxA1 and its peptides each activated formyl peptide receptors in goblet cells. AnxA1 and Ac2-26 at 10 -12 mol/L and Ac2-12 at 10 -9 mol/L inhibited the histamine-stimulated increase in [Ca 2+ ] i , as did resolvin D1 and lipoxin A 4 at 10 -12 mol/L, whereas Ac9-25 did not. AnxA1 and Ac2-26 counter-regulated the H 1 receptor through the p42/p44 mitogen-activated protein kinase/extracellular regulated kinase 1/2, β-adrenergic receptor kinase, and protein kinase C pathways, whereas Ac2-12 counter-regulated only through β-adrenergic receptor kinase. In conclusion, current data show that the N-terminal peptides Ac2-26 and Ac2-12, but not Ac9-25, share multiple functions with the full-length AnxA1 in goblet cells, including inhibition of histamine-stimulated increase in [Ca 2+ ] i and counter-regulation of the H 1  receptor. These actions suggest a potential pharmaceutical application of the AnxA1 N-terminal peptides Ac2-26 and Ac2-12 in homeostasis and ocular inflammatory diseases.
(Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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