scholarly journals Systematic Investigation of Polyurethane Biomaterial Surface Roughness on Human Immune Responses in vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Sören Segan ◽  
Meike Jakobi ◽  
Paree Khokhani ◽  
Sascha Klimosch ◽  
Florian Billing ◽  
...  
Keyword(s):  
Immune Response ◽  
Surface Roughness ◽  
Surface Topography ◽  
Inflammatory Responses ◽  
Hla Dr ◽  
Biomaterial Surface ◽  
Human Immune ◽  
Anti Inflammatory ◽  
The Impact

It has been widely shown that biomaterial surface topography can modulate host immune response, but a fundamental understanding of how different topographies contribute to pro-inflammatory or anti-inflammatory responses is still lacking. To investigate the impact of surface topography on immune response, we undertook a systematic approach by analyzing immune response to eight grades of medical grade polyurethane of increasing surface roughness in three in vitro models of the human immune system. Polyurethane specimens were produced with defined roughness values by injection molding according to the VDI 3400 industrial standard. Specimens ranged from 0.1 μm to 18 μm in average roughness (Ra), which was confirmed by confocal scanning microscopy. Immunological responses were assessed with THP-1-derived macrophages, human peripheral blood mononuclear cells (PBMCs), and whole blood following culture on polyurethane specimens. As shown by the release of pro-inflammatory and anti-inflammatory cytokines in all three models, a mild immune response to polyurethane was observed, however, this was not associated with the degree of surface roughness. Likewise, the cell morphology (cell spreading, circularity, and elongation) in THP-1-derived macrophages and the expression of CD molecules in the PBMC model on T cells (HLA-DR and CD16), NK cells (HLA-DR), and monocytes (HLA-DR, CD16, CD86, and CD163) showed no influence of surface roughness. In summary, this study shows that modifying surface roughness in the micrometer range on polyurethane has no impact on the pro-inflammatory immune response. Therefore, we propose that such modifications do not affect the immunocompatibility of polyurethane, thereby supporting the notion of polyurethane as a biocompatible material.

Ellagitannins, Gallotannins and their Metabolites- The Contribution to the Anti-Inflammatory Effect of Food Products and Medicinal Plants

2019 ◽  
Vol 25 (37) ◽  
pp. 4946-4967 ◽  
Author(s):  
Anna K. Kiss ◽  
Jakub P. Piwowarski
Keyword(s):  
Immune Response ◽  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Health Effects ◽  
Biological Effects ◽  
Food Products ◽  
Anti Inflammatory ◽  
The Impact

The popularity of food products and medicinal plant materials containing hydrolysable tannins (HT) is nowadays rapidly increasing. Among various health effects attributable to the products of plant origin rich in gallotannins and/or ellagitannins the most often underlined is the beneficial influence on diseases possessing inflammatory background. Results of clinical, interventional and animal in vivo studies clearly indicate the antiinflammatory potential of HT-containing products, as well as pure ellagitannins and gallotannins. In recent years a great emphasis has been put on the consideration of metabolism and bioavailability of natural products during examination of their biological effects. Conducted in vivo and in vitro studies of polyphenols metabolism put a new light on this issue and indicate the gut microbiota to play a crucial role in the health effects following their oral administration. The aim of the review is to summarize the knowledge about HT-containing products’ phytochemistry and their anti-inflammatory effects together with discussion of the data about observed biological activities with regards to the current concepts on the HTs’ bioavailability and metabolism. Orally administered HT-containing products due to the limited bioavailability of ellagitannins and gallotannins can influence immune response at the level of gastrointestinal tract as well as express modulating effects on the gut microbiota composition. However, due to the chemical changes being a result of their transit through gastrointestinal tract, comprising of hydrolysis and gut microbiota metabolism, the activity of produced metabolites has to be taken into consideration. Studies regarding biological effects of the HTs’ metabolites, in particular urolithins, indicate their strong and structure-dependent anti-inflammatory activities, being observed at the concentrations, which fit the range of their established bioavailability. The impact of HTs on inflammatory processes has been well established on various in vivo and in vitro models, while influence of microbiota metabolites on silencing the immune response gives a new perspective on understanding anti-inflammatory effects attributed to HT containing products, especially their postulated effectiveness in inflammatory bowel diseases (IBD) and cardiovascular diseases.

scholarly journals Mechanisms Involved in Type II Macrophage Activation and Effector Functions

2021 ◽  
Author(s):  
◽  
Marie Clare Lydia Kharkrang
Keyword(s):  
Immune Responses ◽  
Inflammatory Responses ◽  
Surface Marker ◽  
Alternative Activation ◽  
Type Ii ◽  
Activated Macrophages ◽  
Phenotypic Properties ◽  
Anti Inflammatory ◽  
The Impact

<p>Autoimmunities are extremely difficult to treat and involved in their pathogenesis are pro-inflammatory immune responses redirected against one's own tissues. Studies in our lab have shown macrophages that are induced to become type II macrophages protect against an animal model of MS, experimental autoimmune encephalomyelitis (EAE), with protection due to immune deviation. Another way to deviate immune responses away from inflammation is by infection with the parasitic helminth Schistosoma mansoni, which also protects against EAE. The contribution of type II macrophages in this protection is unknown, as are the mechanisms involved in promoting the phenotype induced by type II activation. This project investigates key mechanisms involved in type II activation, while also elucidating the possible effect of schistosome exposure on the induction of this activation state. Using a validated model of type II activation in vitro, we compared the effects of schistosome immune complexes on various macrophage properties such as cytokine, surface marker and enzymatic profiles. This thesis identified that exposure to schistosome complexes induces a macrophage state with characteristics of two distinct activation states (type II and alternative activation), as well as completely novel characteristics. This activation state shows many phenotypic properties associated with immune regulation, and may have important consequences for understanding mechanisms involved in protection against inflammatory illnesses. We also investigated key mechanisms involved in the anti-inflammatory responses induced by type II activation. Cytokine, chemokine and surface marker profiles of macrophages were assessed in response to type II activation in vitro, with the main emphasis on determining the effects of IL-10 and CD40 on the type II activation phenotype and function. This investigation found that type II activated macrophages depend on low levels of CD40/CD40L signalling to polarise Th2 development, as the expression of receptors for Th2-inducing cytokines are significantly impaired in the absence of this interaction. This suggests an important role for the low but maintained levels of CD40 on type II activated macrophages, in aiding the deviation of immune responses, while maintaining Th2 polarization. We also suggest a suppressive role of CD40/CD40L in IL-10 production, which is a novel find. The requirement of new treatments for MS is escalating as more people are affected each year. The impact of MS on the quality of life is severe and long lasting. Having a greater understanding of the mechanisms involved in deviating pro-inflammatory or anti-inflammatory responses will enable the development of much more effective treatments and therapies in the future.</p>

scholarly journals Host-Directed Therapies: Modulating Inflammation to Treat Tuberculosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Stefanie Krug ◽  
Sadiya Parveen ◽  
William R. Bishai
Keyword(s):  
Immune Response ◽  
Inflammatory Responses ◽  
Lung Damage ◽  
Tb Treatment ◽  
Inflammatory Processes ◽  
Clinical Models ◽  
Human Immune Response ◽  
Human Immune ◽  
Anti Inflammatory ◽  
Microbiological Cure

Following infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), most human hosts are able to contain the infection and avoid progression to active TB disease through expression of a balanced, homeostatic immune response. Proinflammatory mechanisms aiming to kill, slow and sequester the pathogen are key to a successful host response. However, an excessive or inappropriate pro-inflammatory response may lead to granuloma enlargement and tissue damage, which may prolong the TB treatment duration and permanently diminish the lung function of TB survivors. The host also expresses certain anti-inflammatory mediators which may play either beneficial or detrimental roles depending on the timing of their deployment. The balance between the timing and expression levels of pro- and anti-inflammatory responses plays an important role in the fate of infection. Interestingly, M. tuberculosis appears to manipulate both sides of the human immune response to remodel the host environment for its own benefit. Consequently, therapies which modulate either end of this spectrum of immune responses at the appropriate time may have the potential to improve the treatment of TB or to reduce the formation of permanent lung damage after microbiological cure. Here, we highlight host-directed TB therapies targeting pro- or anti-inflammatory processes that have been evaluated in pre-clinical models. The repurposing of already available drugs known to modulate these responses may improve the future of TB therapy.

scholarly journals Modulation of inflammatory responses by Sutherlandia frutescens

2015 ◽  
Author(s):  
◽  
Wei Lei
Keyword(s):  
Aqueous Extract ◽  
Inflammatory Responses ◽  
Ethanolic Extract ◽  
Microbial Activities ◽  
Murine Macrophages ◽  
Oral Consumption ◽  
Anti Inflammatory ◽  
The Impact

Sutherlandia frutescens (L.) R. Br (Lessertia frutescens) is a medicinal plant traditionally used in southern Africa. It has been used for patients suffering from numerous types of cancer, infectious diseases, and various inflammatory conditions. This study was designed to determine the impact of S. frutescens on the inflammatory response and anti-microbial activities on cell and/or animal models. Aqueous and ethanolic extracts of S. frutescens were made and verified using HPLC. These extracts were used to treat murine macrophages (e.g., RAW 264.7 cells and primary macrophages isolated from mice) to evaluate the impact of S. frutescens on in vitro inflammatory responses. This study found that the aqueous extract and a polysaccharide-enriched fraction from the aqueous extract exhibited an immuno-stimulatory activity on murine macrophages. Treatment with aqueous extract or polysaccharides increased the production of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines/chemokines via activating the toll-like receptor 4 signaling pathway. On the other hand, the ethanolic extract of S. frutescens dose-dependently decreased the production of ROS, NO, inducible nitric oxide synthase (iNOS), and various inflammatory cytokines and chemokines in murine macrophages co-stimulated with lipopolysaccharide (LPS) and interferon gamma (IFNy). Follow up experiments demonstrated that the anti-inflammatory activity of the ethanolic extract was mediated via reductions in the activation of NF-kB, extracellular-signal-regulated kinase 1/2 (ERK1/2), and signal transducers and activators of transcription 1 (STAT1). RNA sequencing provided more evidences to support the anti-inflammatory activity of the ethanolic extract of S. frutescens. To our surprise, chlorophylls isolated from S. frutescens had a greater effect on the anti-inflammatory of S. frutescens than that of unique compounds (i.e., sutherlandiosides and sutherlandins). To investigate the impact of oral consumption of S. frutescens on in vivo inflammatory responses and anti-microbial activities, mice were fed with AIN-93G based diet with/without containing ground S. frutescens powder or were gavaged with S. frutescens extracts followed by challenge with E. coli or LPS. These experiments found that oral consumption of S. frutescens had limited or no impact on the in vivo inflammatory responses and anti-microbial activities. Overall, this study provide a better understanding on the beneficial therapeutic properties of S. frutescens using in vitro models, however these studies in a laboratory mouse model suggest that consumption of S. frutescens had only a modest impact on host anti-microbial and inflammatory responses to a gram-negative microbial challenge whether intact microbes or bacterial endotoxin (i.e., LPS) was used.

scholarly journals Mechanisms Involved in Type II Macrophage Activation and Effector Functions

2021 ◽  
Author(s):  
◽  
Marie Clare Lydia Kharkrang
Keyword(s):  
Immune Responses ◽  
Inflammatory Responses ◽  
Surface Marker ◽  
Alternative Activation ◽  
Type Ii ◽  
Activated Macrophages ◽  
Phenotypic Properties ◽  
Anti Inflammatory ◽  
The Impact

<p>Autoimmunities are extremely difficult to treat and involved in their pathogenesis are pro-inflammatory immune responses redirected against one's own tissues. Studies in our lab have shown macrophages that are induced to become type II macrophages protect against an animal model of MS, experimental autoimmune encephalomyelitis (EAE), with protection due to immune deviation. Another way to deviate immune responses away from inflammation is by infection with the parasitic helminth Schistosoma mansoni, which also protects against EAE. The contribution of type II macrophages in this protection is unknown, as are the mechanisms involved in promoting the phenotype induced by type II activation. This project investigates key mechanisms involved in type II activation, while also elucidating the possible effect of schistosome exposure on the induction of this activation state. Using a validated model of type II activation in vitro, we compared the effects of schistosome immune complexes on various macrophage properties such as cytokine, surface marker and enzymatic profiles. This thesis identified that exposure to schistosome complexes induces a macrophage state with characteristics of two distinct activation states (type II and alternative activation), as well as completely novel characteristics. This activation state shows many phenotypic properties associated with immune regulation, and may have important consequences for understanding mechanisms involved in protection against inflammatory illnesses. We also investigated key mechanisms involved in the anti-inflammatory responses induced by type II activation. Cytokine, chemokine and surface marker profiles of macrophages were assessed in response to type II activation in vitro, with the main emphasis on determining the effects of IL-10 and CD40 on the type II activation phenotype and function. This investigation found that type II activated macrophages depend on low levels of CD40/CD40L signalling to polarise Th2 development, as the expression of receptors for Th2-inducing cytokines are significantly impaired in the absence of this interaction. This suggests an important role for the low but maintained levels of CD40 on type II activated macrophages, in aiding the deviation of immune responses, while maintaining Th2 polarization. We also suggest a suppressive role of CD40/CD40L in IL-10 production, which is a novel find. The requirement of new treatments for MS is escalating as more people are affected each year. The impact of MS on the quality of life is severe and long lasting. Having a greater understanding of the mechanisms involved in deviating pro-inflammatory or anti-inflammatory responses will enable the development of much more effective treatments and therapies in the future.</p>

scholarly journals Gain-of-Function Mutation of Tristetraprolin Impairs Negative Feedback Control of Macrophages In Vitro yet Has Overwhelmingly Anti-Inflammatory Consequences In Vivo

2017 ◽  
Vol 37 (11) ◽  
Author(s):  
John D. O'Neil ◽  
Ewan A. Ross ◽  
Michael L. Ridley ◽  
Qize Ding ◽  
Tina Tang ◽  
...  
Keyword(s):  
Feedback Control ◽  
Negative Feedback ◽  
Inflammatory Responses ◽  
Interleukin 10 ◽  
Gain Of Function ◽  
Negative Feedback Control ◽  
Anti Inflammatory ◽  
The Impact

ABSTRACT The mRNA-destabilizing factor tristetraprolin (TTP) binds in a sequence-specific manner to the 3′ untranslated regions of many proinflammatory mRNAs and recruits complexes of nucleases to promote rapid mRNA turnover. Mice lacking TTP develop a severe, spontaneous inflammatory syndrome characterized by the overexpression of tumor necrosis factor and other inflammatory mediators. However, TTP also employs the same mechanism to inhibit the expression of the potent anti-inflammatory cytokine interleukin 10 (IL-10). Perturbation of TTP function may therefore have mixed effects on inflammatory responses, either increasing or decreasing the expression of proinflammatory factors via direct or indirect mechanisms. We recently described a knock-in mouse strain in which the substitution of 2 amino acids of the endogenous TTP protein renders it constitutively active as an mRNA-destabilizing factor. Here we investigate the impact on the IL-10-mediated anti-inflammatory response. It is shown that the gain-of-function mutation of TTP impairs IL-10-mediated negative feedback control of macrophage function in vitro. However, the in vivo effects of TTP mutation are uniformly anti-inflammatory despite the decreased expression of IL-10.

scholarly journals Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  
Keyword(s):  
Immune Response ◽  
Hematological Malignancies ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Tnf Α ◽  
Monocytes And Macrophages ◽  
Ifn Γ ◽  
And Function ◽  
The Impact

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

scholarly journals NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Major Gene ◽  
Critical Role ◽  
Orthotopic Model ◽  
Independent Manner ◽  
Maternal Immune Response ◽  
The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

scholarly journals Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 328 ◽  
Author(s):  
Claudio Salaris ◽  
Melania Scarpa ◽  
Marina Elli ◽  
Alice Bertolini ◽  
Simone Guglielmetti ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Plaque Assay ◽  
Immune Response Gene ◽  
Intestinal Epithelial ◽  
Antiviral Immune Response ◽  
Qrt Pcr ◽  
Anti Inflammatory

SARS-CoV-2 is a newly emerging virus that currently lacks curative treatments. Lactoferrin (LF) is a naturally occurring non-toxic glycoprotein with broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. In this study, we assessed the potential of LF in the prevention of SARS-CoV-2 infection in vitro. Antiviral immune response gene expression was analyzed by qRT-PCR in uninfected Caco-2 intestinal epithelial cells treated with LF. An infection assay for SARS-CoV-2 was performed in Caco-2 cells treated or not with LF. SARS-CoV-2 titer was determined by qRT-PCR, plaque assay and immunostaining. Inflammatory and anti-inflammatory cytokine production was determined by qRT-PCR. LF significantly induced the expression of IFNA1, IFNB1, TLR3, TLR7, IRF3, IRF7 and MAVS genes. Furthermore, LF partially inhibited SARS-CoV-2 infection and replication in Caco-2 intestinal epithelial cells. Our in vitro data support LF as an immune modulator of the antiviral immune response with moderate effects against SARS-CoV-2 infection.

scholarly journals The impact of indole-3-lactic acid on immature intestinal innate immunity and development: a transcriptomic analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wuyang Huang ◽  
Ky Young Cho ◽  
Di Meng ◽  
W. Allan Walker
Keyword(s):  
Lactic Acid ◽  
Mechanistic Model ◽  
Transcriptomic Analysis ◽  
Dependent Manner ◽  
Protective Effects ◽  
Very Preterm Infants ◽  
Anti Inflammatory ◽  
The Impact

AbstractAn excessive intestinal inflammatory response may have a role in the pathogenesis of necrotizing enterocolitis (NEC) in very preterm infants. Indole-3-lactic acid (ILA) of breastmilk tryptophan was identified as the anti-inflammatory metabolite involved in probiotic conditioned media from Bifidobacteria longum subsp infantis. This study aimed to explore the molecular endocytic pathways involved in the protective ILA effect against inflammation. H4 cells, Caco-2 cells, C57BL/6 pup and adult mice were used to compare the anti-inflammatory mechanisms between immature and mature enterocytes in vitro and in vivo. The results show that ILA has pleiotropic protective effects on immature enterocytes including anti-inflammatory, anti-viral, and developmental regulatory potentials in a region-dependent and an age-dependent manner. Quantitative transcriptomic analysis revealed a new mechanistic model in which STAT1 pathways play an important role in IL-1β-induced inflammation and ILA has a regulatory effect on STAT1 pathways. These studies were validated by real-time RT-qPCR and STAT1 inhibitor experiments. Different protective reactions of ILA between immature and mature enterocytes indicated that ILA’s effects are developmentally regulated. These findings may be helpful in preventing NEC for premature infants.

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