Decellularized Porcine Achilles Tendon Induces Anti-inflammatory Macrophage Phenotype In Vitro and Tendon Repair In Vivo

Abstract Background: Early strut coverage after sirolimus-eluting stent (SES) implantation is associated with the activation of inflammation, but the underlying mechanisms are not completely understood. The present study aimed to identify the relationship between the anti-inflammatory cytokine interleukin (IL) 35 (IL-35) and early strut coverage in vivo and in vitro. Methods: We utilized a retrospective study design to measure IL-35 levels in 68 stents from 68 patients with coronary artery disease and recorded serial optical coherence tomography (OCT) images (0 and 3 months) to assess stent endothelialization. The mechanism underlying the regulatory effects of IL-35 on macrophages and human umbilical vein endothelial cells (HUVECs) was also investigated. SESs were surgically implanted into the right common carotid arteries of 200 male New Zealand White rabbits receiving intravenous injections of IL-35 or a placebo. Results: At the 3-month OCT evaluation, complete endothelium coverage was correlated with IL-35 levels. IL-35 induced the activation of an anti-inflammatory M2-like macrophage phenotype by targeting the signal transducer and activators of transcription (STAT)1/4 signalling pathway, and IL-35-treated macrophages induced endothelial proliferation and alleviated endothelial dysfunction. IL-35-treated New Zealand White rabbits with implanted SESs showed lower percentages of cross-sections with an uncovered strut, elevated mean neointimal hyperplasia (NIH) thickness, and inhibited inflammatory responses. Conclusions: We investigated the effect of IL-35 expression on early stent endothelialization in vivo and in vitro and identified a crucial role for IL-35 in inducing the activation of an anti-inflammatory M2-like macrophage phenotype. The present study highlights a new therapeutic strategy for early stent endothelialization.

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Statins Directly Influence the Polarization of Adipose Tissue Macrophages: A Role in Chronic Inflammation

Biomedicines ◽

10.3390/biomedicines9020211 ◽

2021 ◽

Vol 9 (2) ◽

pp. 211

Author(s):

Sona Kauerova ◽

Hana Bartuskova ◽

Barbora Muffova ◽

Libor Janousek ◽

Jiri Fronek ◽

...

Keyword(s):

Adipose Tissue ◽

Ldl Cholesterol ◽

Macrophage Polarization ◽

Inflammatory Activity ◽

Human Macrophage ◽

Macrophage Phenotype ◽

Anti Inflammatory ◽

Inflammatory Macrophages ◽

Inflammatory Macrophage

Statins represent one of the most widely used classes of drugs in current medicine. In addition to a substantial decrease in atherogenic low density lipoprotein (LDL) particle concentrations, several large trials have documented their potent anti-inflammatory activity. Based on our preliminary data, we showed that statins are able to decrease the proportion of pro-inflammatory macrophages (CD14+16+CD36high) in visceral adipose tissue in humans. In the present study including 118 healthy individuals (living kidney donors), a very close relationship between the pro-inflammatory macrophage proportion and LDL cholesterol levels was found. This was confirmed after adjustment for the most important risk factors. The effect of statins on the proportion of pro-inflammatory macrophages was also confirmed in an experimental model of the Prague hereditary hypercholesterolemia rat. A direct anti-inflammatory effect of fluvastatin on human macrophage polarization in vitro was documented. Based on modifying the LDL cholesterol concentrations, statins are suggested to decrease the cholesterol inflow through the lipid raft of macrophages in adipose tissue and hypercholesterolemia to enhance the pro-inflammatory macrophage phenotype polarization. On the contrary, due to their opposite effect, statins respond with anti-inflammatory activity, affecting the whole organism.

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IRF5 Is a Specific Marker of Inflammatory MacrophagesIn Vivo

Mediators of Inflammation ◽

10.1155/2013/245804 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 63

Author(s):

Miriam Weiss ◽

Katrina Blazek ◽

Adam J. Byrne ◽

Dany P. Perocheau ◽

Irina A. Udalova

Keyword(s):

Specific Marker ◽

M2 Macrophages ◽

Macrophage Phenotype ◽

Tissue Remodelling ◽

Murine Bone Marrow ◽

Macrophage Polarisation ◽

M1 Macrophage ◽

Anti Inflammatory

Macrophages are an integral part of the innate immune system and key players in pathogen clearance and tissue remodelling. Both functions are accomplished by a pivotal network of different macrophage subtypes, including proinflammatory M1 and anti-inflammatory M2 macrophages. Previously, our laboratory identified the transcription factor interferon regulatory factor 5 (IRF5) as the master regulator of the M1 macrophage polarisation. IRF5 was found to be highly expressed in human M1 compared to M2 macrophages. Furthermore, IRF5 dictates the expression of proinflammatory genes such asIL12bandIL23awhilst repressing anti-inflammatory genes likeIL10. Here we show that murine bone marrow derived macrophages differentiatedin vitrowith GM-CSF are also characterised by high levels of IRF5 mRNA and protein and express proinflammatory cytokines upon LPS stimulation. These macrophages display characteristic expression of M1-marker MHC II but lack the M2-marker CD206. Significantly, we develop intracellular staining of IRF5- expressing macrophages and utilise it to recapitulate thein vitroresults in anin vivomodel of antigen-induced arthritis, emphasising their physiological relevance. Thus, we establish the species-invariant role of IRF5 in controlling the inflammatory macrophage phenotype bothin vitroand inin vivo.

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Achilles Tendon Repair by Decellularized and Engineered Xenografts in a Rabbit Model

Stem Cells International ◽

10.1155/2019/5267479 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14

Author(s):

Marta Bottagisio ◽

Daniele D’Arrigo ◽

Giuseppe Talò ◽

Matilde Bongio ◽

Marco Ferroni ◽

...

Keyword(s):

Achilles Tendon ◽

Rabbit Model ◽

Tendon Repair ◽

Perfusion Culture ◽

Autologous Bone Marrow ◽

Type I ◽

Tendon Reconstruction ◽

The Matrix

Tendon tissue ruptures often require the replacement of damaged tissues. The use of auto- or allografts is notoriously limited due to the scarce supply and the high risks of immune adverse reactions. To overcome these limitations, tissue engineering (TE) has been considered a promising approach. Among several biomaterials, decellularized xenografts are available in large quantity and could represent a possible solution for tendon reconstruction. The present study is aimed at evaluating TE xenografts in Achilles tendon defects. Specifically, the ability to enhance the biomechanical functionality, while improving the graft interaction with the host, was tested. The combination of decellularized equine-derived tendon xenografts with or without the matrix repopulation with autologous bone marrow mesenchymal stem cells (BMSCs) under stretch-perfusion dynamic conditions might improve the side-to-side tendon reconstruction. Thirty-six New Zealand rabbits were used to create 2 cm long segmental defects of the Achilles tendon. Then, animals were implanted with autograft (AG) as the gold standard control, decellularized graft (DG), or in vitro tissue-engineered graft (TEG) and evaluated postoperatively at 12 weeks. After sacrifice, histological, immunohistochemical, biochemical, and biomechanical analyses were performed along with the matrix metalloproteinases. The results demonstrated the beneficial role of undifferentiated BMSCs loaded within decellularized xenografts undergoing a stretch-perfusion culture as an immunomodulatory weapon reducing the inflammatory process. Interestingly, AG and TEG groups exhibited similar results, behaved similarly, and showed a significant superior tissue healing compared to DG in terms of newly formed collagen fibres and biomechanical parameters. Whereas, DG demonstrated a massive inflammatory and giant cell response associated with graft destruction and necrosis, absence of type I and III collagen, and a higher amount of proteoglycans and MMP-2, thus unfavourably affecting the biomechanical response. In conclusion, this in vivo study suggests a potential use of the proposed tissue-engineered constructs for tendon reconstruction.

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AMPKα1 is essential for Glucocorticoid Receptor triggered anti-inflammatory macrophage activation

10.1101/2020.01.02.892836 ◽

2020 ◽

Author(s):

Giorgio Caratti ◽

Thibaut Desgeorges ◽

Gaëtan Juban ◽

Mascha Koenen ◽

Bozhena Kozak ◽

...

Keyword(s):

Glucocorticoid Receptor ◽

Transcriptional Control ◽

Inflammatory Cells ◽

Macrophage Phenotype ◽

Post Injury ◽

Inflammatory Phase ◽

Anti Inflammatory ◽

Amp Activated Protein Kinase ◽

Inflammatory Macrophage

SummaryMacrophages are key immune cells which mediate both the acute inflammatory phase and the repair phase after tissue damage. Macrophages switch from pro-inflammatory to anti-inflammatory cells that sustain repair and return to tissue homeostasis. We show that the metabolic sensor, AMP-activated protein kinase (AMPK) is essential for glucocorticoid induction of an anti-inflammatory macrophage phenotype. While canonical gene regulation by glucocorticoids was not affected by loss of AMPK, we identified AMPK-dependent glucocorticoid-regulated genes in macrophages, related to efferocytosis. AMPK-deficient macrophages do not acquire phenotypic and functional anti-inflammatory features upon glucocorticoid exposure. We identified FOXO3 as an AMPK-dependent regulator of glucocorticoid activity in macrophages. Loss of AMPK in macrophages in vivo abrogates glucocorticoid anti-inflammatory actions during post-injury muscle regeneration and endotoxin induced acute lung injury. These data highlight that the glucocorticoid receptor is dependent on AMPK for its immunomodulatory actions in macrophages, linking their metabolic status to transcriptional control in resolving inflammation.

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In vitro and in vivo evaluation of the anti-inflammatory effects of Arzanol from Helichrysum italicum

Planta Medica ◽

10.1055/s-0030-1264369 ◽

2010 ◽

Vol 76 (12) ◽

Author(s):

J Bauer ◽

F Dehm ◽

A Koeberle ◽

F Pollastro ◽

G Appendino ◽

...

Keyword(s):

In Vivo Evaluation ◽

Anti Inflammatory

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Haemanthus coccineus extract shows profound anti-inflammatory actions in vitro and in vivo due to its main alkaloid narciclasine

Planta Medica ◽

10.1055/s-0035-1565331 ◽

2015 ◽

Vol 81 (16) ◽

Author(s):

S Fuchs ◽

LT Hsieh ◽

W Saarberg ◽

CAJ Erdelmeier ◽

TA Wichelhaus ◽

...

Keyword(s):

Anti Inflammatory

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Reprogrammed M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 extends lifespan of mice with experimental carcinoma

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2017.02.4-9 ◽

2017 ◽

pp. 4-9

Author(s):

С.В. Калиш ◽

С.В. Лямина ◽

А.А. Раецкая ◽

И.Ю. Малышев

Keyword(s):

Tumor Growth ◽

Culture Medium ◽

Ehrlich Carcinoma ◽

Macrophage Phenotype ◽

M1 Macrophages ◽

M1 Macrophage ◽

Ec Cells ◽

Experimental Carcinoma

Цель исследования. Репрограммирование М1 фенотипа макрофагов с ингибированными факторами транскрипции М2 фенотипа STAT3, STAТ6 и SMAD и оценка их влияния на развитие карциномы Эрлиха (КЭ) in vitro и in vivo. Методика. Рост опухоли иницировали in vitro путем добавления клеток КЭ в среду культивирования RPMI-1640 и in vivo путем внутрибрюшинной инъекции клеток КЭ мышам. Результаты. Установлено, что M1макрофаги и in vitro, и in vivo оказывают выраженный противоопухолевый эффект, который превосходит антиопухолевые эффекты М1, M1, M1 макрофагов и цисплатина. Заключение. М1 макрофаги с ингибированными STAT3, STAT6 и/или SMAD3 эффективно ограничивают рост опухоли. Полученные данные обосновывают разработку новой технологии противоопухолевой клеточной терапии. Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo . Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1 macrophages have a pronounced anti-tumor effect in vitro , and in vivo , which was greater than anti-tumor effects of M1, M1, M1 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

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