scholarly journals Roles of Specialized Pro-Resolving Lipid Mediators in Autophagy and Inflammation

2020 ◽  
Vol 21 (18) ◽  
pp. 6637 ◽  
Author(s):  
Antonio Recchiuti ◽  
Elisa Isopi ◽  
Mario Romano ◽  
Domenico Mattoscio
Keyword(s):  
Inflammatory Response ◽  
Cytokine Production ◽  
Lipid Mediators ◽  
Tissue Homeostasis ◽  
Leukocyte Infiltration ◽  
Catabolic Pathway ◽  
Resolution Of Inflammation ◽  
Endogenous Lipid ◽  
Inflammation Resolution ◽  
Cellular Components

Autophagy is a catabolic pathway that accounts for degradation and recycling of cellular components to extend cell survival under stress conditions. In addition to this prominent role, recent evidence indicates that autophagy is crucially involved in the regulation of the inflammatory response, a tightly controlled process aimed at clearing the inflammatory stimulus and restoring tissue homeostasis. To be efficient and beneficial to the host, inflammation should be controlled by a resolution program, since uncontrolled inflammation is the underlying cause of many pathologies. Resolution of inflammation is an active process mediated by a variety of mediators, including the so-called specialized pro-resolving lipid mediators (SPMs), a family of endogenous lipid autacoids known to regulate leukocyte infiltration and activities, and counterbalance cytokine production. Recently, regulation of autophagic mechanisms by these mediators has emerged, uncovering unappreciated connections between inflammation resolution and autophagy. Here, we summarize mechanisms of autophagy and resolution, focusing on the contribution of autophagy in sustaining paradigmatic examples of chronic inflammatory disorders. Then, we discuss the evidence that SPMs can restore dysregulated autophagy, hypothesizing that resolution of inflammation could represent an innovative approach to modulate autophagy and its impact on the inflammatory response.

scholarly journals Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Gabriel Dasilva ◽  
Salomé Lois ◽  
Lucía Méndez ◽  
Bernat Miralles-Pérez ◽  
Marta Romeu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Response ◽  
White Adipose Tissue ◽  
Lipid Mediators ◽  
Tissue Homeostasis ◽  
Enzymatic Oxidation ◽  
Fish Oils ◽  
Compensatory Mechanism ◽  
Epa And Dha

Adipose tissue is now recognized as an active organ with an important homeostatic function in glucose and lipid metabolism and the development of insulin resistance. The present research investigates the role of lipid mediators and lipid profiling for controlling inflammation and the metabolic normal function of white adipose tissue from rats suffering from diet-induced prediabetes. Additionally, the contribution to the adipose lipidome induced by the consumption of marine ω-3 PUFAs as potential regulators of inflammation is addressed. For that, the effects on the inflammatory response triggered by high-fat high-sucrose (HFHS) diets were studied in male Sprague-Dawley rats. Using SPE-LC-MS/MS-based metabolo-lipidomics, a range of eicosanoids, docosanoids and specialized pro-resolving mediators (SPMs) were measured in white adipose tissue. The inflammatory response occurring in prediabetic adipose tissue was associated with the decomposition of ARA epoxides to ARA-dihydroxides, the reduction of oxo-derivatives and the formation of prostaglandins (PGs). In an attempt to control the inflammatory response initiated, LOX and non-enzymatic oxidation shifted toward the production of the less pro-inflammatory EPA and DHA metabolites rather than the high pro-inflammatory ARA hydroxides. Additionally, the change in LOX activity induced the production of intermediate hydroxides precursors of SPMs as protectins (PDs), resolvins (Rvs) and maresins (MaRs). This compensatory mechanism to achieve the restoration of tissue homeostasis was significantly strengthened through supplementation with fish oils. Increasing proportions of ω-3 PUFAs in adipose tissue significantly stimulated the formation of DHA-epoxides by cytochrome P450, the production of non-enzymatic EPA-metabolites and prompted the activity of 12LOX. Finally, protectin PDX was significantly reduced in the adipose tissue of prediabetic rats and highly enhanced through ω-3 PUFAs supplementation. Taken together, these actively coordinated modifications constitute key mechanisms to restore adipose tissue homeostasis with an important role of lipid mediators. This compensatory mechanism is reinforced through the supplementation of the diet with fish oils with high and balanced contents of EPA and DHA. The study highlights new insides on the targets for effective treatment of incipient diet-induced diabetes and the mechanism underlying the potential anti-inflammatory action of marine lipids.

scholarly journals Cytokine gene regulation by PGE2, LTB4and PAF

1992 ◽  
Vol 1 (1) ◽  
pp. 5-8 ◽  
Author(s):  
M. Rola-Pleszczynski ◽  
J. Stankova
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Gene Regulation ◽  
Inflammatory Response ◽  
Cytokine Production ◽  
Initial Response ◽  
Lipid Mediators ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Regulatory Effects

The initial response of the host to noxious stimuli produces a nonspecific inflammatory response. A more specific immune response is believed to be modulated by two classes of molecules: lipid mediators (PG, LT and PAF) and cytokines, synthesized by phagocytes and parenchyreal cells. In this review we discuss the increasing evidence of the interrelationship between eicosanoids, PAF and cytokines: IL-1 and TNF induce PG synthesis in various cells and PG, in turn, modulate cytokine production. We focused on the regulatory effects ofLTB4,PGE2and PAF on cytokine gene expression.

scholarly journals Specialized Pro-Resolving Mediators as Potential Regulators of Inflammatory Macrophage Responses in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria G. Balta ◽  
Evangelos Papathanasiou ◽  
Panagiotis F. Christopoulos
Keyword(s):  
Cytokine Production ◽  
Lipid Mediators ◽  
Economic Consequences ◽  
Macrophage Infiltration ◽  
Cytokine Storm ◽  
Macrophage Phenotype ◽  
Resolution Of Inflammation ◽  
Molecular Events ◽  
Recent Outbreak ◽  
Inflammatory Macrophage

The recent outbreak of SARS-CoV2 has emerged as one of the biggest pandemics of our century, with outrageous health, social and economic consequences globally. Macrophages may lay in the center of COVID-19 pathogenesis and lethality and treatment of the macrophage-induced cytokine storm has emerged as essential. Specialized pro-resolving mediators (SPMs) hold strong therapeutic potentials in the management of COVID-19 as they can regulate macrophage infiltration and cytokine production but also promote a pro-resolving macrophage phenotype. In this review, we discuss the homeostatic functions of SPMs acting directly on macrophages on various levels, towards the resolution of inflammation. Moreover, we address the molecular events that link the lipid mediators with COVID-19 severity and discuss the clinical potentials of SPMs in COVID-19 immunotherapeutics.

scholarly journals RvD1 accelerates the resolution of inflammation by promoting apoptosis of the recruited macrophages via the ALX/FasL-FasR/caspase-3 signaling pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shu-yang Xiang ◽  
Yang Ye ◽  
Qian Yang ◽  
Hao- ran Xu ◽  
Chen-xi Shen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Caspase 3 ◽  
Distress Syndrome ◽  
Inflammatory Factors ◽  
Lipid Mediator ◽  
Resolvin D1 ◽  
Resolution Of Inflammation ◽  
Inflammatory Monocytes ◽  
Endogenous Lipid ◽  
Inflammation Resolution

AbstractThe uncontrolled inflammatory response caused by a disorder in inflammation resolution is one of the reasons for acute respiratory distress syndrome (ARDS). The macrophage pool markedly expands when inflammatory monocytes, known as recruited macrophages, migrate from the circulation to the lung. The persistent presence of recruited macrophages leads to chronic inflammation in the resolution phase of inflammation. On the contrary, elimination of the recruited macrophages at the injury site leads to the rapid resolution of inflammation. Resolvin D1 (RvD1) is an endogenous lipid mediator derived from docosahexaenoic acid. Mice were administered RvD1 via the tail vein 3 and 4 days after stimulation with lipopolysaccharide. RvD1 reduced the levels of the inflammatory factors in the lung tissue, promoted the anti-inflammatory M2 phenotype, and enhanced the phagocytic function of recruited macrophages to alleviate acute lung injury. We also found that the number of macrophages was decreased in BAL fluid after treatment with RvD1. RvD1 increased the apoptosis of recruited macrophages partly via the FasL-FasR/caspase-3 signaling pathway, and this effect could be blocked by Boc-2, an ALX/PRP2 inhibitor. Taken together, our findings reinforce the concept of therapeutic targeting leading to the apoptosis of recruited macrophages. Thus, RvD1 may provide a new therapy for the resolution of ARDS.

Cyane-carvone, a Synthetic Derivative of Carvone, Inhibits Inflammatory Response by Reducing Cytokine Production and Oxidative Stress and Shows Antinociceptive Effect in Mice

Inflammation ◽  
2014 ◽  
Author(s):  
Thiago Henrique Costa Marques ◽  
Maria Leonildes Boavista Gomes Cast Marques ◽  
Jand-Venes R. Medeiros ◽  
Renan Oliveira Silva ◽  
André Luiz dos Reis Barbosa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Cytokine Production ◽  
Antinociceptive Effect ◽  
Synthetic Derivative ◽  
And Oxidative Stress

scholarly journals Effect of pregnancy hormone mixtures on cytokine production and surface marker expression in naïve and LPS-activated THP-1 differentiated monocytes/macrophages

2019 ◽  
Vol 26 (2) ◽  
pp. 84-96
Author(s):  
María Isabel Mendoza-Cabrera ◽  
Rosa-Elena Navarro-Hernández ◽  
Anne Santerre ◽  
Pablo Cesar Ortiz-Lazareno ◽  
Ana Laura Pereira-Suárez ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cytokine Production ◽  
Immune Cell ◽  
Surface Marker ◽  
Independent Manner ◽  
Surface Marker Expression ◽  
Monocytes And Macrophages ◽  
Marker Expression ◽  
Activated Monocytes ◽  
In Pregnancy

In pregnancy, maternal monocytes and macrophages acquire a specific phenotype that enables them to maintain immune tolerance and facilitate hormone–immune cell interactions, which are necessary for gestational progression. The aim of this study was to determine the effect of pregnancy hormone mixtures of the first and third trimesters on both resting and activated monocytes and macrophages. Pregnancy hormone levels (cortisol, estradiol, progesterone, and prolactin) were quantified at the first and third trimesters. The average of the levels obtained was used to prepare two mixtures of synthetic hormones: low and high. These mixtures were then used to stimulate THP-1 monocytes and macrophages, resting or activated with LPS. Cytokine production in the culture supernatants and surface marker expression (CD14, CD86, and CD163) were evaluated by ELISA and flow cytometry, respectively. We found that the hormones modulated the pro-inflammatory response of THP-1 cells, LPS-activated monocytes, and macrophages, inducing high levels of IL-10 and low levels of IL-8, IL-1-β, and IL-6. All hormone stimulation increased the CD163 receptor in both resting and LPS-activated monocytes and macrophages in a dose-independent manner, unlike CD14 and CD86. Pregnancy hormones promote the expression of the markers associated with the M2-like phenotype, modulating their pro-inflammatory response. This phenotype regulation by hormones could be a determinant in pregnancy.

scholarly journals A dynamic equilibrium between TTP and CPEB4 controls mRNA stability and inflammation resolution

2021 ◽  
Author(s):  
Clara Suñer ◽  
Annarita Sibilio ◽  
Judit Martín ◽  
Chiara Lara Castellazzi ◽  
Oscar Reina ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mrna Stability ◽  
Regulatory Network ◽  
Dynamic Equilibrium ◽  
Relative Number ◽  
Mapk Signalling Pathway ◽  
Mapk Signalling ◽  
Inflammation Resolution

SUMMARYTemporal control of inflammation is critical to avoid pathological developments, and is largely defined through the differential stabilities of mRNAs. While TTP-directed mRNA deadenylation is known to destabilize ARE-containing mRNAs, this mechanism alone cannot explain the variety of mRNA expression kinetics observed during inflammation resolution. Here we show that inflammation resolution requires CPEB4 expression, in vitro and in vivo. Our results identify that CPEB4-directed polyadenylation and TTP-mediated deadenylation compete during the resolutive phase of the LPS response to uncouple the degradation of pro-inflammatory mRNAs from the sustained expression of anti-inflammatory mRNAs. The outcome of this equilibrium is quantitatively defined by the relative number of CPEs and AREs in each mRNA, and further shaped by the coordinated regulation by the MAPK signalling pathway of the levels and activities of their trans-acting factors, CPEB4 and TTP. Altogether, we describe a temporal- and transcript-specific regulatory network controlling the extent of the inflammatory response.

scholarly journals Zdhhc2 Is Essential for Plasmacytoid Dendritic Cells Mediated Inflammatory Response in Psoriasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Binhui Zhou ◽  
Wenyi Yang ◽  
Wushan Li ◽  
Le He ◽  
Liaoxun Lu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Plasmacytoid Dendritic Cell ◽  
White Blood Cells ◽  
Psoriatic Skin ◽  
Interferon Α ◽  
Inflammatory Disorder ◽  
Post Translational Modification ◽  
Cellular Components ◽  
Deficient Mice

Zdhhc family genes are composed of 24 members that regulate palmitoylation, a post-translational modification process for proteins. Mutations in genes that alter palmitoylation or de-palmitoylation could result in neurodegenerative diseases and inflammatory disorders. In this study, we found that Zdhhc2 was robustly induced in psoriatic skin and loss of Zdhhc2 in mice by CRISPR/Cas9 dramatically inhibited pathology of the ear skin following imiquimod treatment. As psoriasis is an inflammatory disorder, we analyzed tissue infiltrating immune cells and cytokine production. Strikingly we found that a master psoriatic cytokine interferon-α (IFN-α) in the lesioned skin of wildtype (WT) mice was 23-fold higher than that in Zdhhc2 deficient counterparts. In addition, we found that CD45+ white blood cells (WBC) infiltrating in the skin of Zdhhc2 deficient mice were also significantly reduced. Amelioration in psoriasis and dramatically reduced inflammation of Zdhhc2 deficient mice led us to analyze the cellular components that were affected by loss of Zdhhc2. We found that imiquimod induced plasmacytoid dendritic cell (pDC) accumulation in psoriatic skin, spleen, and draining lymph nodes (DLN) were drastically decreased in Zdhhc2 deficient mice, and the expression of pDC activation marker CD80 also exhibited significantly inhibited in psoriatic skin. In further experiments, we confirmed the cell intrinsic effect of Zdhhc2 on pDCs as we found that loss of zDHHC2 in human CAL-1 pDC dampened both interferon regulatory factor 7 (IRF7) phosphorylation and IFN-α production. Therefore, we identified novel function of Zdhhc2 in controlling inflammatory response in psoriasis in mice and we also confirmed that crucial role of Zdhhc2 in pDCs by regulating IRF7 activity and production of the critical cytokine. Our results finding the dependence of IFN-α production on Zdhhc2 in inflamed murine skin and in human pDCs provide rationale for targeting this new molecule in treatment of inflammation.

scholarly journals Endogenous Receptor Agonists: Resolving Inflammation

2007 ◽  
Vol 7 ◽  
pp. 1440-1462 ◽  
Author(s):  
Gerhard Bannenberg ◽  
Makoto Arita ◽  
Charles N. Serhan
Keyword(s):  
Fatty Acids ◽  
Essential Fatty Acids ◽  
Tissue Level ◽  
Lipid Mediators ◽  
Recent Advances ◽  
Molecular Events ◽  
Inflammation Resolution ◽  
Specific Lipid ◽  
Chemical Mediators

Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA)–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

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