A Novel Effect for Annexin 1-Derived Peptide Ac2-26: Reduction of Allergic Inflammation in the Rat

Abstract

Previous investigations have provided evidence that the Nterminal peptide of annexin 1 (peptide Ac2-26) has the capacity of reproducing the anti-inflammatory actions of the full-length protein in many systems. In the current study, we report the effectiveness of the peptide Ac2-26 as an antiallergic tool in a model of rat pleurisy and provide indication for some of the mechanisms involved. In rats inflamed by injection of ovalbumin into the pleural cavity 14 days postsensitization, peptide Ac2-26 (50 -200 g/cavity) inhibited mast cell degranulation, plasma protein leakage, and the accumulation of both neutrophils and eosinophils. Treatment with either peptide Ac2-26 (200 g/cavity) or dexamethasone (1 mg/kg i.p.) inhibited ovalbumin-induced eotaxin release in the pleural effluents. In vitro, peptide Ac2-26 inhibited ovalbumin-evoked histamine release from subcutaneous tissue fragments obtained from sensitized rats (33-66 M) and interleukin-13-evoked eotaxin generation from cultured rat mesothelial cells (16 -33 M) but not eosinophil chemotaxis. This work demonstrates that the annexin 1 mimetic peptide Ac2-26 prevents allergen-evoked eosinophilic inflammatory response in rats. Combined analysis of the in vivo and in vitro experiments presented herein suggests that the blockade of secretion of pivotal mediators for the allergic response, such as histamine and eotaxin, could be responsible for the inhibitory actions displayed by peptide Ac2-26.

Annexin-A1 Regulates TLR-Mediated IFN-β Production through an Interaction with TANK-Binding Kinase 1

“…In the current study, we demonstrate that ANXA1 acts as key component of the TLR signaling pathway in macrophages, particularly driving the TRIF-dependent TLR cascade and the expression of IFN-inducible cytokines/chemokines involved in the innate immune response. ANXA1 has been found to have antiinflammatory and anti-migratory effects in several models in vitro and in vivo (9,10,29). In contrast to its well-characterized antiinflammatory properties, our results suggest ANXA1 as an essential mediator of TLR-induced inflammation.…”

Annexin 1: Differential expression in tumor and mast cells in human larynx cancer

“…18,42 Also local administration of the ANXA1 N-terminal peptide inhibits mast cell degranulation in rats inflamed by infection of ovalbumin into the pleural cavity. 19 The increase in ANXA1 expression observed in mast cells in the tumor and peritumoral region compared to control tissue, suggests that the endogenous protein may act as a feedback response in the modulation of mediators release. Since mast cells mediators have a role in cancer growth, ANXA1 may contribute to the modulation of mediators release.…”

“…Mast cells can be beneficial or detrimental to the tumor depending on the tumor stroma microenvironment altering its secretory process. 25 A number of studies have provided evidence that mast cells express the anti-inflammatory protein ANXA1 18,19,42 and this protein has been implicated in playing an important role in tumor development, directly or indirectly, and could be a diagnostic marker for certain types of tumors. 7 Our results have demonstrated the intracellular localization and disposition of human mast cell ANXA1 by ultrastructural immunocytochemical analysis in laryngeal tissues (tumor, peritumoral and control tissues) obtained from the same patient.…”

“…8 ANXA1 also has been reported in inflammatory cells, particularly in mast cells involved in the inflammatory responses. 18,19 Mast cells have been reported in various types of the cancer such as breast, 20 skin, 21 liver 22 and gastric. 23 These cells accumulate at sites of tumor growth in response to numerous chemoattractants.…”

Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles

“…In this study, we investigated the delivery and bioactions of polymeric NPs encapsulating Ac2-26, an annexin A1 N-terminal 25 amino acid mimetic peptide that acts on the G-protein-coupled formyl peptide receptor, ALX/FPR2, which is also the receptor for lipoxin A4 (7,20,21). Ac2-26 exerts anti-inflammatory (22) and proresolving actions in vivo and was shown to be protective in several disease models, including myocardial ischemia-reperfusion injury (23), allergic inflammation (24), and endotoxin-induced cerebral inflammation (25).…”