In vitro phenotypic effects of Lipoxin A4 on M1 and M2 polarized macrophages derived from THP-1

Aubeux, Davy; Tessier, Solène; Pérez, Fabienne; Geoffroy, Valérie; Gaudin, Alexis

doi:10.1007/s11033-022-08041-5

Cited by 4 publications

(4 citation statements)

References 41 publications

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“…properties. Previous studies have demonstrated the anti-inflammatory effect of LXA4 on various cell types, such as stem cells from the apical papilla [26] and macrophages [5].…”

Section: Discussionmentioning

confidence: 99%

“…Among SPMs, lipoxin A4 (LXA4), derived from arachidonic acid, serves as an immune modulatory mediator with the capacity to attenuate monocytes recruitment and to induce a pro resolving M2 phenotype [5,6]. In light of these properties, numerous studies have evaluated the therapeutic potential of this molecule for conditions such as asthma, metabolic disease, arthritis, pain, diabetic wound healing, vascular conditions including peripheral artery disease and aortic aneurysm and periodontitis [1,[7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Influence of physico-chemical properties of two lipoxin emulsion-loaded hydrogels on pre-polarized macrophages: a comparative analysis

Guyon,

Tessier,

Croyal

et al. 2024

Drug Deliv. and Transl. Res.

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Inflammation, a crucial defense mechanism, must be rigorously regulated to prevent the onset of chronic inflammation and subsequent tissue damage. Specialized pro resolving mediators (SPMs) such as lipoxin A4 (LXA4) have demonstrated their ability to facilitate the resolution of inflammation by orchestrating a transition of M1 pro-inflammatory macrophages towards an anti-inflammatory M2 phenotype. However, the hydrophobic and chemically labile nature of LXA4 necessitates the development of a delivery system capable of preserving its integrity for clinical applications. In this study, two types of emulsion were formulated using different homogenization processes (mechanical overhead stirrer (ME) or Luer-lock syringes (SE)).Following characterization, including size and droplet morphology assessment by microscopy, the encapsulation efficiency (EE) was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). To exert control over LXA4 release, these emulsions were embedded within silanized hyaluronic acid hydrogels. A comprehensive evaluation, encompassing gel time, swelling, and degradation profiles under acidic, basic, and neutral conditions, preceded the assessment of LXA4 cumulative release using LC-MS/MS.Physicochemical results indicate that H-ME exhibits superior efficiency over H-SE. While both formulations stimulated pro-inflammatory cytokine secretion and promoted a proinflammatory macrophage phenotype, LXA4 emulsion-loaded hydrogels displayed a diminished pro-inflammatory activity compared to blank emulsion-loaded hydrogels. These findings highlight the biological efficacy of LXA4 within both systems, with H-SE 4 outperforming H-ME in terms of efficiency. These versatile H-ME and H-SE formulations can be customized to enhance their biological activity making them promising tools to promote the resolution of inflammation in diverse clinical applications.

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“…properties. Previous studies have demonstrated the anti-inflammatory effect of LXA4 on various cell types, such as stem cells from the apical papilla [26] and macrophages [5].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of physico-chemical properties of two lipoxin emulsion-loaded hydrogels on pre-polarized macrophages: a comparative analysis

Guyon,

Tessier,

Croyal

et al. 2024

Drug Deliv. and Transl. Res.

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“…LXA 4 has differential actions in M1 and M2 macrophages. LXA 4 reduces the gene expression of pro-inflammatory cytokines in M1 macrophages and increases the IL-10 mRNA expression in M2 macrophages derived from THP-1 cells ( 89 ). LXA 4 also induces M2 polarization in a model of osteoarthritis ( 90 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms

et al. 2023

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BackgroundLipoxin A4 (LXA4) has anti-inflammatory and pro-resolutive roles in inflammation. We evaluated the effects and mechanisms of action of LXA4 in titanium dioxide (TiO2) arthritis, a model of prosthesis-induced joint inflammation and pain.MethodsMice were stimulated with TiO2 (3mg) in the knee joint followed by LXA4 (0.1, 1, or 10ng/animal) or vehicle (ethanol 3.2% in saline) administration. Pain-like behavior, inflammation, and dosages were performed to assess the effects of LXA4in vivo.ResultsLXA4 reduced mechanical and thermal hyperalgesia, histopathological damage, edema, and recruitment of leukocytes without liver, kidney, or stomach toxicity. LXA4 reduced leukocyte migration and modulated cytokine production. These effects were explained by reduced nuclear factor kappa B (NFκB) activation in recruited macrophages. LXA4 improved antioxidant parameters [reduced glutathione (GSH) and 2,2-azino-bis 3-ethylbenzothiazoline-6-sulfonate (ABTS) levels, nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and Nrf2 protein expression], reducing reactive oxygen species (ROS) fluorescent detection induced by TiO2 in synovial fluid leukocytes. We observed an increase of lipoxin receptor (ALX/FPR2) in transient receptor potential cation channel subfamily V member 1 (TRPV1)+ DRG nociceptive neurons upon TiO2 inflammation. LXA4 reduced TiO2‐induced TRPV1 mRNA expression and protein detection, as well TRPV1 co-staining with p-NFκB, indicating reduction of neuronal activation. LXA4 down-modulated neuronal activation and response to capsaicin (a TRPV1 agonist) and AITC [a transient receptor potential ankyrin 1 (TRPA1) agonist] of DRG neurons.ConclusionLXA4 might target recruited leukocytes and primary afferent nociceptive neurons to exert analgesic and anti-inflammatory activities in a model resembling what is observed in patients with prosthesis inflammation.

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Section: Introductionmentioning

confidence: 99%

Influence of Physico-Chemical Properties of Two Lipoxin Emulsion-Loaded Hydrogels on Pre-Polarized Macrophages: A Comparative Analysis

Guyon,

Tessier,

Croyal

et al. 2024

Preprint

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Inflammation, a crucial defense mechanism, must be rigorously regulated to prevent the onset of chronic inflammation and subsequent tissue damage. Specialized pro resolving mediators (SPMs) such as lipoxin A4 (LXA4) have demonstrated their ability to facilitate the resolution of inflammation by orchestrating a transition of M1 pro-inflammatory macrophages towards an anti-inflammatory M2 phenotype. However, the hydrophobic and chemically labile nature of LXA4 necessitates the development of a delivery system capable of preserving its integrity for clinical applications. In this study, two types of emulsion were formulated using different homogenization processes (mechanical overhead stirrer (ME) or Luer-lock syringes (SE)). Following characterization, including size and droplet morphology assessment by microscopy, the encapsulation efficiency (EE) was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). To exert control over LXA4 release, these emulsions were embedded within silanized hyaluronic acid hydrogels. A comprehensive evaluation, encompassing gel time, swelling, and degradation profiles under acidic, basic, and neutral conditions, preceded the assessment of LXA4 cumulative release using LC-MS/MS. Physicochemical results indicate that H-ME exhibits superior efficiency over H-SE. While both formulations stimulated pro-inflammatory cytokine secretion and promoted a pro-inflammatory macrophage phenotype, LXA4 emulsion-loaded hydrogels displayed a diminished pro-inflammatory activity compared to blank emulsion-loaded hydrogels. These findings highlight the biological efficacy of LXA4 within both systems, with H-SE outperforming H-ME in terms of efficiency. These versatile H-ME and H-SE formulations can be customized to enhance their biological activity making them promising tools to promote the resolution of inflammation in diverse clinical applications.

show abstract

In vitro phenotypic effects of Lipoxin A4 on M1 and M2 polarized macrophages derived from THP-1

Cited by 4 publications

References 41 publications

Influence of physico-chemical properties of two lipoxin emulsion-loaded hydrogels on pre-polarized macrophages: a comparative analysis

Influence of physico-chemical properties of two lipoxin emulsion-loaded hydrogels on pre-polarized macrophages: a comparative analysis

Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms

Influence of Physico-Chemical Properties of Two Lipoxin Emulsion-Loaded Hydrogels on Pre-Polarized Macrophages: A Comparative Analysis

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