scholarly journals PGE2 production at sites of tissue injury promotes an anti-inflammatory neutrophil phenotype and determines the outcome of inflammation resolution in vivo

2018 ◽  
Vol 4 (9) ◽  
pp. eaar8320 ◽  
Author(s):  
Catherine A. Loynes ◽  
Jou A. Lee ◽  
Anne L. Robertson ◽  
Michael JG. Steel ◽  
Felix Ellett ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Pge2 Production ◽  
Anti Inflammatory ◽  
Inflammation Resolution

scholarly journals PGE2 production at sites of tissue injury promotes an anti-inflammatory neutrophil phenotype and determines the outcome of inflammation resolution in vivo

2017 ◽  
Author(s):  
Catherine A. Loynes ◽  
Jou A. Lee ◽  
Anne L. Robertson ◽  
Michael JG. Steel ◽  
Felix Ellett ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Neutrophil Migration ◽  
Chronic Inflammatory Disease ◽  
Lipid Mediator ◽  
Prostaglandin E ◽  
Zebrafish Model ◽  
Reverse Migration ◽  
Anti Inflammatory ◽  
Inflammation Resolution

AbstractNeutrophils are the first immune cells recruited to a site of injury or infection, where they perform many functions. Having completed their role, neutrophils must be removed from the inflammatory site - either by apoptosis and efferocytosis or by reverse migration away from the wound - for restoration of normal tissue homeostasis. Disruption of these tightly controlled physiological processes of neutrophil removal can lead to a range of inflammatory diseases. We used an in vivo zebrafish model to understand the role of lipid mediator production in neutrophil removal. Following tailfin amputation in the absence of macrophages, neutrophillic inflammation does not resolve. This is due to loss of macrophage-dependent production of eicosanoid prostaglandin E2, which drives neutrophil removal via promotion of reverse migration. Knockdown of endogenous prostaglandin E synthase gene reveals PGE2 as essential for neutrophil inflammation resolution. Furthermore, PGE2 is able to signal through EP4 receptors to enhance Alox15 production, causing a switch towards anti-inflammatory eicosanoid signalling, specifically Lipoxin A4. Our data confirm regulation of neutrophil migration by PGE2 and LXA4 in an in vivo model of inflammation resolution. This pathway may contain therapeutic targets for driving inflammation resolution in chronic inflammatory disease.

scholarly journals Osthole Protects against Acute Lung Injury by Suppressing NF-κB-Dependent Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yiyi Jin ◽  
Jianchang Qian ◽  
Xin Ju ◽  
Xiaodong Bao ◽  
Li Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Nuclear Translocation ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Peritoneal Macrophages ◽  
Anti Inflammatory

Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.

scholarly journals Fundamentally different roles of neuronal TNF receptors in CNS pathology: TNFR1 and IKKβ promote microglial responses and tissue injury in demyelination while TNFR2 protects against excitotoxicity in mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Irini Papazian ◽  
Eleni Tsoukala ◽  
Athena Boutou ◽  
Maria Karamita ◽  
Konstantinos Kambas ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Neuroprotective Effect ◽  
Glutamate Excitotoxicity ◽  
Tnf Receptors ◽  
Neuroprotective Effects ◽  
Cns Diseases ◽  
Cns Pathology ◽  
Anti Inflammatory

Abstract Background During inflammatory demyelination, TNF receptor 1 (TNFR1) mediates detrimental proinflammatory effects of soluble TNF (solTNF), whereas TNFR2 mediates beneficial effects of transmembrane TNF (tmTNF) through oligodendroglia, microglia, and possibly other cell types. This model supports the use of selective inhibitors of solTNF/TNFR1 as anti-inflammatory drugs for central nervous system (CNS) diseases. A potential obstacle is the neuroprotective effect of solTNF pretreatment described in cultured neurons, but the relevance in vivo is unknown. Methods To address this question, we generated mice with neuron-specific depletion of TNFR1, TNFR2, or inhibitor of NF-κB kinase subunit β (IKKβ), a main downstream mediator of TNFR signaling, and applied experimental models of inflammatory demyelination and acute and preconditioning glutamate excitotoxicity. We also investigated the molecular and cellular requirements of solTNF neuroprotection by generating astrocyte-neuron co-cultures with different combinations of wild-type (WT) and TNF and TNFR knockout cells and measuring N-methyl-d-aspartate (NMDA) excitotoxicity in vitro. Results Neither neuronal TNFR1 nor TNFR2 protected mice during inflammatory demyelination. In fact, both neuronal TNFR1 and neuronal IKKβ promoted microglial responses and tissue injury, and TNFR1 was further required for oligodendrocyte loss and axonal damage in cuprizone-induced demyelination. In contrast, neuronal TNFR2 increased preconditioning protection in a kainic acid (KA) excitotoxicity model in mice and limited hippocampal neuron death. The protective effects of neuronal TNFR2 observed in vivo were further investigated in vitro. As previously described, pretreatment of astrocyte-neuron co-cultures with solTNF (and therefore TNFR1) protected them against NMDA excitotoxicity. However, protection was dependent on astrocyte, not neuronal TNFR1, on astrocyte tmTNF-neuronal TNFR2 interactions, and was reproduced by a TNFR2 agonist. Conclusions These results demonstrate that neuronal TNF receptors perform fundamentally different roles in CNS pathology in vivo, with neuronal TNFR1 and IKKβ promoting microglial inflammation and neurotoxicity in demyelination, and neuronal TNFR2 mediating neuroprotection in excitotoxicity. They also reveal that previously described neuroprotective effects of solTNF against glutamate excitotoxicity in vitro are indirect and mediated via astrocyte tmTNF-neuron TNFR2 interactions. These results consolidate the concept that selective inhibition of solTNF/TNFR1 with maintenance of TNFR2 function would have combined anti-inflammatory and neuroprotective properties required for safe treatment of CNS diseases.

scholarly journals The CXCL12/CXCR4 signalling axis retains neutrophils at inflammatory sites in zebrafish

2019 ◽  
Author(s):  
Hannah M. Isles ◽  
Kimberly Herman ◽  
Anne L. Robertson ◽  
Catherine A. Loynes ◽  
Lynne R. Prince ◽  
...  
Keyword(s):  
Inflammatory Disease ◽  
Tissue Damage ◽  
Tissue Injury ◽  
Transgenic Zebrafish ◽  
Sequencing Data ◽  
Cxcr4 Antagonist ◽  
Reverse Migration ◽  
Zebrafish Larvae ◽  
Inflammation Resolution

AbstractThe inappropriate retention of neutrophils in the lung is a major driver of the excessive tissue damage characteristic of respiratory inflammatory diseases including COPD, ARDS and cystic fibrosis. The molecular programmes which orchestrate neutrophil recruitment to inflammatory sites through chemotactic guidance have been well studied. However, how neutrophil sensitivity to these cues is modulated during inflammation resolution is not understood. The identification of neutrophil reverse migration as a mechanism of inflammation resolution and the ability to modulate this therapeutically has identified a new target to treat inflammatory disease. Here we investigate the role of the CXCL12/CXCR4 signalling axis in modulating neutrophil retention at inflammatory sites. We used an in vivo tissue injury model to study inflammation using transgenic zebrafish larvae. Expression of cxcl12a and cxcr4b during the tissue damage response was assessed using in situ hybridisation and analysis of RNA sequencing data. CRISPR/Cas9 was used to knockdown cxcl12a and cxcr4b in zebrafish larvae. The CXCR4 antagonist AMD3100 was used to block the Cxcl12/Cxcr4 signalling axis pharmacologically. We identified that cxcr4b and cxcl12a are expressed at the wound site in zebrafish larvae during the inflammatory response. Following tail-fin transection, removal of neutrophils from inflammatory sites is significantly increased in cxcr4b and cxcl12a CRISPR knockdown larvae. Pharmacological inhibition of the Cxcl12/Cxcr4 signalling axis accelerates inflammation resolution, an effect caused by an increase in neutrophil reverse migration. The findings of this study suggest that CXCR4/CXCL12 signalling may play an important role in neutrophil retention at inflammatory sites, identifying a potential new target for the therapeutic removal of neutrophils from the lung in chronic inflammatory disease.

scholarly journals Cinnamon and Eucalyptus Oils Suppress the Inflammation Induced by Lipopolysaccharide In Vivo

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7410
Author(s):  
Chen Zhao ◽  
Yuwei Cao ◽  
Zhuo Zhang ◽  
Dechao Nie ◽  
Yanling Li
Keyword(s):  
Tissue Injury ◽  
Body Weight Gain ◽  
Animal Health ◽  
Interleukin 10 ◽  
Necrosis Factor Alpha ◽  
Cinnamon Oil ◽  
Eucalyptus Oil ◽  
Tnf Α ◽  
Anti Inflammatory

Inflammation caused by bacterial lipopolysaccharide (LPS) disrupts epithelial homeostasis and threatens both human and animal health. Therefore, the discovery and development of new anti-inflammatory drugs is urgently required. Plant-derived essential oils (EOs) have good antioxidant and anti-inflammatory activities. Thus, this study aims to screen and evaluate the effects of cinnamon oil and eucalyptus oil on anti-inflammatory activities. The associated evaluation indicators include body weight gain, visceral edema coefficient, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitrogen monoxide (NO), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), Urea, Crea, ALT, TLR4, MyD88, NF-κB, IκB-α, iNOS, and Mn-SOD. In addition, tissue injury was determined by H&E staining. The results revealed that cinnamon oil and eucalyptus oil suppressed inflammation by decreasing SOD, TNF-α, and NF-κB levels. We also found that cinnamon oil increased the level of GSH-Px, MDA, and Mn-SOD, as well as the visceral edema coefficient of the kidney and liver. Altogether, these findings illustrated that cinnamon oil and eucalyptus oil exhibited wide antioxidant and anti-inflammatory activities against LPS-induced inflammation.

scholarly journals Activation of hypoxia-inducible factor-1α (Hif-1α) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 712-722 ◽  
Author(s):  
Philip M. Elks ◽  
Fredericus J. van Eeden ◽  
Giles Dixon ◽  
Xingang Wang ◽  
Constantino Carlos Reyes-Aldasoro ◽  
...  
Keyword(s):  
Cell Function ◽  
Genetic Manipulation ◽  
Tissue Injury ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Site Directed Mutagenesis ◽  
Neutrophil Apoptosis ◽  
Hypoxia Inducible Factor 1Α ◽  
Inflammation Resolution

Abstract The oxygen-sensing transcription factor hypoxia-inducible factor-1α (HIF-1α) plays a critical role in the regulation of myeloid cell function. The mechanisms of regulation are not well understood, nor are the phenotypic consequences of HIF modulation in the context of neutrophilic inflammation. Species conservation across higher metazoans enables the use of the genetically tractable and transparent zebrafish (Danio rerio) embryo to study in vivo resolution of the inflammatory response. Using both a pharmacologic approach known to lead to stabilization of HIF-1α, and selective genetic manipulation of zebrafish HIF-1α homologs, we sought to determine the roles of HIF-1α in inflammation resolution. Both approaches reveal that activated Hif-1α delays resolution of inflammation after tail transection in zebrafish larvae. This delay can be replicated by neutrophil-specific Hif activation and is a consequence of both reduced neutrophil apoptosis and increased retention of neutrophils at the site of tissue injury. Hif-activated neutrophils continue to patrol the injury site during the resolution phase, when neutrophils would normally migrate away. Site-directed mutagenesis of Hif in vivo reveals that hydroxylation of Hif-1α by prolyl hydroxylases critically regulates the Hif pathway in zebrafish neutrophils. Our data demonstrate that Hif-1α regulates neutrophil function in complex ways during inflammation resolution in vivo.

scholarly journals Angiotensin-(1-7) and Alamandine Promote Anti-inflammatory Response in Macrophages In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Melissa de Carvalho Santuchi ◽  
Miriane Fernandes Dutra ◽  
Juliana Priscila Vago ◽  
Kátia Maciel Lima ◽  
Izabela Galvão ◽  
...  
Keyword(s):  
Immune Cell ◽  
Inflammatory Diseases ◽  
Renin Angiotensin System ◽  
M1 Macrophages ◽  
Macrophage Phenotypes ◽  
Anti Inflammatory ◽  
Inflammation Resolution ◽  
Macrophage Subsets

The renin-angiotensin system (RAS) peptides play an important role in inflammation. Resolution of inflammation contributes to restore tissue homeostasis, and it is characterized by neutrophil apoptosis and their subsequent removal by macrophages, which are remarkable plastic cells involved in the pathophysiology of diverse inflammatory diseases. However, the effects of RAS peptides on different macrophage phenotypes are still emerging. Here, we evaluated the effects of angiotensin-(1-7) (Ang-(1-7)) and the most novel RAS peptide, alamandine, on resting (M0), proinflammatory M(LPS+IFN-γ), and anti-inflammatory M(IL-4) macrophage phenotypes in vitro, as well as on specific immune cell populations and macrophage subsets into the pleural cavity of LPS-induced pleurisy in mice. Our results showed that Ang-(1-7) and alamandine, through Mas and MrgD receptors, respectively, do not affect M0 macrophages but reduce the proinflammatory TNF-α, CCL2, and IL-1β transcript expression levels in LPS+IFN-γ-stimulated macrophages. Therapeutic administration of these peptides in LPS-induced inflammation in mice decreased the number of neutrophils and M1 (F4/80lowGr1+CD11bmed) macrophage frequency without affecting the other investigated macrophage subsets. Our data suggested that both Ang-(1-7) and alamandine, through their respective receptors Mas and MrgD, promote an anti-inflammatory reprogramming of M(LPS+IFN-γ)/M1 macrophages under inflammatory circumstances and potentiate the reprogramming induced by IL-4. In conclusion, our work sheds light on the emerging proresolving properties of Ang-(1-7) and alamandine, opening new avenues for the treatment of inflammatory diseases.

New bicyclic [3.2.1] octane neolignans derivatives from Aniba firmula with potent in vivo anti-inflammatory activity on account of dual inhibition of PGE2 production and cell recruitment

2019 ◽  
Vol 30 ◽  
pp. 31-37 ◽  
Author(s):  
Mario F.C. Santos ◽  
Bianca G.V. Alcântara ◽  
Cristiane dos R. Feliciano ◽  
Aline F. Silva ◽  
Tatiane C.S. Maiolini ◽  
...  
Keyword(s):  
Pge2 Production ◽  
Inflammatory Activity ◽  
Cell Recruitment ◽  
Dual Inhibition ◽  
Anti Inflammatory

Heme Oxygenase-1 Production by Peripheral Blood Monocytes During Acute Inflammatory Illnesses of Children

2003 ◽  
Vol 228 (5) ◽  
pp. 550-556 ◽  
Author(s):  
Akihiro Yachie ◽  
Tomoko Toma ◽  
Kazunori Mizuno ◽  
Hiroyuki Okamoto ◽  
Shoetsu Shimura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Polymerase Chain Reaction ◽  
Heme Oxygenase ◽  
Tissue Injury ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Anti Inflammatory

Monocytes play key roles both in innate and adaptive antigen-specific immunity and they constitute critical components of the immune responses. Although most of the monocyte-derived cytokines exhibit proinflammatory functions in vivo, heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, exerts potent anti-inflammatory effect through production of carbon monoxide and bilirubin. We compared HO-1 production by monocytes in vivo in various acute inflammatory illnesses and in normal controls. Freshly isolated monocytes produced little HO-1 as detected by immunohistochemistry, but it was rapidly induced in vitro upon stimulation. HO-1 production by monocytes was selective because it was not induced in other leukocyte populations, including granulocytes and lymphocytes. Monocytes from acute inflammatory illnesses, such as Kawasaki disease and acute infectious diseases, viral or bacterial, produced significant levels of HO-1, as detected by flow cytometry, immunohistochemistry, and reverse transcription polymerase chain reaction. Quantitative analysis of HO-1 mRNA expression by real-time polymerase chain reaction revealed that monocytes from controls exhibited low, but significant levels of HO-1 mRNA, indicating that circulating monocytes produce HO-1 constantly, in response to basal level of oxidative stress encountered daily. Significantly elevated HO-1 mRNA levels seen in acute inflammatory illnesses suggest that monocyte HO-1 production serve as potent anti-inflammatory agent to control excessive cell or tissue injury in the presence of oxidative stress and cytokinemia.

scholarly journals UJI IN VIVO TAHAP PREKLINIS TERHADAP EKSTRAK BATANG PISANG (Musa paradisiaca L.) SEBAGAI ANTIINFLAMASI TOPIKAL

2021 ◽  
Vol 3 (2) ◽  
pp. 138-151
Author(s):  
Ni Luh Kade Arman Anita Dewi ◽  
Putu Era Sandhi Kusuma Yuda ◽  
I Gede Agus Suarnata ◽  
Maria Malida Vernandes Sasadara
Keyword(s):  
Tissue Injury ◽  
Negative Control ◽  
Male Rats ◽  
Control Group ◽  
Musa Paradisiaca ◽  
Stem Extract ◽  
Anti Inflammatory ◽  
Banana Stem ◽  
Inflammatory Effect

Inflammation is a normal protective response to tissue injury caused by physical trauma, chemical damage, or microbiological substances. Banana stems (Musa paradisiaca L.) have been empirically believed for their topical anti-inflammatory properties. The purpose of this study was to scientifically evaluate the in vivo preclinical anti-inflammatory activity of banana stems. This research was designed experimentally using twenty-five albino male rats which were divided into five groups: the positive control group which received sodium diclofenac gel, the negative control group which received gel basis preparation without any active ingredient, and three experimental groups which received banana stem extract gel in three different concentrations, 5%, 10%, and 15%. Every five rats of every group were firstly injected with 1% of carrageenan, and the anti-inflammatory effect was evaluated every hour for 4 hours using a plethysmometer.  The collected data were statistically evaluated. The results showed that banana stem extract gel with concentrations of 15% produced the best anti-inflammatory effect, compared to other gel concentrations. In conclusion, the preparation of 15% banana stem extract gel can be applied as potential topical anti-inflammatory preparation.

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