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Papers of the Week

Papers: 8 Jul 2023 - 14 Jul 2023

Basic Science

In Vitro Studies, Molecular/Cellular, Pharmacology/Drug Development

Inflammation/Inflammatory, Orofacial/Head Pain

2023 Jul 07

Am J Pathol


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.


Lyngstadaas AV, Olsen MV, Bair J, Yang M, Hodges RR, Utheim TP, Serhan CN, Dartt DA


Annexin A1 (AnxA1) is the main 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] ([Ca]) 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] caused by AnxA1 and its N-terminal peptides in goblet cells was measured to determine which formyl peptide receptors (FPRs) the compounds use and the action of the peptides on histamine stimulation. Changes in [Ca] were determined using a fluorescent Ca indicator. AnxA1 and its peptides each activated FPRs in goblet cells. AnxA1 and Ac2-26 at 10 M and Ac2-12 at 10 M inhibited the histamine-stimulated increase in [Ca] as did RvD1 and LXA at 10 M, while Ac9-25 did not. AnxA1 and Ac2-26 counter-regulated the H1 receptor through the p42p44MAPK/ERK1/2, β-adrenergic receptor kinase (βARK) and protein kinase C (PKC) pathways, whereas Ac2-12 counter-regulated only through βARK. In conclusion, 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] and counter-regulation of the H1 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.