scholarly journals IN VITRO EXPERIMENTAL REWIRING OF 4 NEUTROPHILIC GRANULOCYTE SUBSETS FROM THE PRO-INFLAMMATORY TO THE ANTI-INFLAMMATORY PHENOTYPE IN CHILDREN WITH SURGICAL PURULENT INFECTION OF SOFT TISSUE

2021 ◽  
Vol 23 (4) ◽  
pp. 819-824
Author(s):  
I. V. Nesterova ◽  
G. A. Chudilova ◽  
V. N. Pavlenko ◽  
V. A. Tarakanov
Keyword(s):  
Soft Tissue ◽  
Young Children ◽  
Functional Activity ◽  
Aureus Strain ◽  
Healthy Children ◽  
Phagocytic Function ◽  
In Vitro System ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Treatment of young children with atypical or recurrent purulent soft tissue infections (PSTD) that do not respond well to surgery and antibiotics is most challenging. PSTD occurs against the background of impaired functioning of the immune system and, first of all, the system of neutrophilic granulocytes (NG). The vector effect of immunotropic therapy on a specific NG subsets may allow the correction of NG dysfunctions without compromising host protection, including strategies to enhance, inhibit or restore their functions.The aim of study: to evaluate in vitro the modulating effects of arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine (HP) on the transformed phenotype of 4 NG subsets, as well as on the functional activity of NG in children with purulent-inflammatory soft tissue diseases.We studied samples of peripheral blood (PB) from young children 2-4 years old: 17 children with atypical acute PSTD and 10 apparently healthy children. At stage I, a comparative assessment of the content and phenotype of 4 NG subsets CD16+CD62L+СD63- , CD16+CD62L+СD63+, СD64- CD16+CD32+CD11b+, СD64+CD16+CD32+CD11b+, phagocytic and microbicidal functions of NG was carried out. At stage II, the in vitro system determined the effects of HP on NG in children with PSTD according to the studied parameters. By the method of flow cytometry (FC500 “Beckman Coulter” (USA), conjugates of MkAT “Beckman Coulter International S.A.” (France)), the relative number of NGs of the studied subsets and the density of receptor expression (MFI) were determined. To assess the phagocytic function of NG a microbiological method was used to assess the completeness of phagocytosis with S. aureus (strain 209). The activity of NG NADPH oxidase was investigated in the NBT-spontaneous test (NBTsp.) and in the in vitro NBT-induced test (NBTind.). A comparative study of PB samples from conventionally healthy children and children with PSTD made it possible to identify various variants of transformation of the phenotype of the studied NG subsets, associated with defects in their functional activity. In the in vitro system the effects of HP were demonstrated, manifested by a decrease in the amount of CD16+CD62L+CD63+NG and an increase in CD16+CD62L+CD63- NG, modulation of the negatively altered phenotype of subsets CD64- CD32+CD16+CD11b+NG and CD64+CD32+CD16+CD11b+NG, aimed at restoring phagocytic function and maintaining the tension of NADPH oxidases.As a result of the study it was found the immunomodulatory effects of HP, which is manifested in the reorientation of NG from the pro-inflammatory phenotype to the anti-inflammatory one, which can be used in the future when creating personalized targeted immunotherapy aimed at correcting defective functioning NG in early children, suffering from PSTD. 

EFFECT OF MULTIPOTENT MESENCHYMAL STROMAL CELLS ON THE FUNCTIONAL ACTIVITY OF MONOCYTE-DERIVED MACROPHAGES UNDER A SHORT-TERM HYPOXIC STRESS IN VITRO

2021 ◽  
Vol 55 (5) ◽  
pp. 45-52
Author(s):  
O.Yu. Alekseeva ◽  
◽  
P.I. Bobyleva ◽  
E.R. Andreeva ◽  
◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Functional Activity ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Hypoxic Stress ◽  
Hypoxic Conditions ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

We studied interactions of mesenchymal stromal cells (MSCs) and cells from the monocyte-macrophage group (MN/MP) important in the MSCs mediated therapeutic action in vivo, their anti-inflammatory and immunomodulating properties. The MSCs effect on the MN/MP functional activity was evaluated after a 6-d co-culture in standard conditions (20 % О2) and ensuing exposure of one part of MN/MP and MN/MP+MSCs to a long-term hypoxic stress (1 % О2, 24 hrs) while the other part remained at 20 % О2. As in the normal, so hypoxic conditions the MSCs stromal activity contributed to the MN/MP viability by decreasing the numbers of MN/MP cells during early apoptosis. The paracrine interaction in 20 % О2 occurred with an elevated MN/MP phagocytic activity without influence on the lysosomal compartment activity. The hypoxic stress affected the MSCs-induced phagocytic ability and activity of lysosomes. Interaction with MSCs leads to formation of a MN/MP anti-inflammatory phenotype that unveils the phagocytic potential in the presence of MSCs despite the oxygen deprivation.

scholarly journals Anti-Inflammatory and Immunomodulatory Effects of the Grifola frondosa Natural Compound o-Orsellinaldehyde on LPS-Challenged Murine Primary Glial Cells. Roles of NF-κβ and MAPK

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 806
Author(s):  
Sarah Tomas-Hernandez ◽  
Jordi Blanco ◽  
Santiago Garcia-Vallvé ◽  
Gerard Pujadas ◽  
María José Ojeda-Montes ◽  
...  
Keyword(s):  
Natural Compound ◽  
Underlying Disease ◽  
Grifola Frondosa ◽  
Beneficial Effects ◽  
Inflammatory Conditions ◽  
Inflammatory Mechanism ◽  
Inflammatory Phenotype ◽  
Mice Brain ◽  
Anti Inflammatory

In response to foreign or endogenous stimuli, both microglia and astrocytes adopt an activated phenotype that promotes the release of pro-inflammatory mediators. This inflammatory mechanism, known as neuroinflammation, is essential in the defense against foreign invasion and in normal tissue repair; nevertheless, when constantly activated, this process can become detrimental through the release of neurotoxic factors that amplify underlying disease. In consequence, this study presents the anti-inflammatory and immunomodulatory properties of o-orsellinaldehyde, a natural compound found by an in silico approach in the Grifola frondosa mushroom, in astrocytes and microglia cells. For this purpose, primary microglia and astrocytes were isolated from mice brain and cultured in vitro. Subsequently, cells were exposed to LPS in the absence or presence of increasing concentrations of this natural compound. Specifically, the results shown that o-orsellinaldehyde strongly inhibits the LPS-induced inflammatory response in astrocytes and microglia by decreasing nitrite formation and downregulating iNOS and HO-1 expression. Furthermore, in microglia cells o-orsellinaldehyde inhibits NF-κB activation; and potently counteracts LPS-mediated p38 kinase and JNK phosphorylation (MAPK). In this regard, o-orsellinaldehyde treatment also induces a significant cell immunomodulation by repolarizing microglia toward the M2 anti-inflammatory phenotype. Altogether, these results could partially explain the reported beneficial effects of G. frondosa extracts on inflammatory conditions.

scholarly journals A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV-2 at the immune–epithelial interface

2021 ◽  
Vol 119 (1) ◽  
pp. e2116853118
Author(s):  
Juliette Leon ◽  
Daniel A. Michelson ◽  
Judith Olejnik ◽  
Kaitavjeet Chowdhary ◽  
Hyung Suk Oh ◽  
...  
Keyword(s):  
Influenza A ◽  
Ebola Virus ◽  
Multiorgan Failure ◽  
Healthy Children ◽  
Nonstructural Proteins ◽  
Strong Response ◽  
Mechanistic Insight ◽  
Inflammatory Phenotype ◽  
Transcriptional Induction

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight and ferret out the root of this immune dysregulation, we modeled, by in vitro coculture, the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV-2–specific inflammatory gene cluster distinct from that seen in influenza A or Ebola virus-infected cocultures, and which reproduced deviations reported in blood or lung myeloid cells from COVID-19 patients. A substantial fraction of the effect could be reproduced after individual transfection of several SARS-CoV-2 proteins (Spike and some nonstructural proteins), mediated by soluble factors, but not via transcriptional induction. This response was greatly muted in monocytes from healthy children, perhaps a clue to the age dependency of COVID-19. These results suggest that the inflammatory malfunction in COVID-19 is rooted in the earliest perturbations that SARS-CoV-2 induces in epithelia.

scholarly journals Natural Glycoside Salidroside Ameliorates Orthopedic Surgery-Induced Cognitive Dysfunction Through Activating Adenosine 5‘-Monophosphate-Activated Protein Kinase Signaling in Mice

2021 ◽  
Author(s):  
Cai-Long Pan ◽  
Guo-Liang Dai ◽  
Hui-Wen Zhang ◽  
Chen-Yang Zhang ◽  
Qing-Hai Meng ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Orthopedic Surgery ◽  
Neurological Diseases ◽  
Docking Studies ◽  
Morris Water Maze Test ◽  
Ampk Pathway ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Abstract Background: Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Salidroside, a plant-derived compound, has gained increased attention as treatment for various neurological diseases and particularly modifier of microglia-mediated neuroinflammation. However, the effect of salidroside on orthopedic surgery-induced cognitive dysfunction and the underlying mechanisms are largely unknown.Methods: The Morris water maze test was used to investigate potential effects of salidroside in the animal model of tibia fracturing with intramedullary fixation. Therapeutic mechanism and related signaling pathways of salidroside in PND were further investigated with animal tissues and microglial cultures in vitro by molecular biology tests.Results: Here we found that salidroside greatly attenuated cognitive impairment in mice after orthopedic surgery. Neuroinflammation in mouse hippocampus were also attenuated by salidroside. Meanwhile, salidroside treatment induced a switch in microglia polarization to the anti-inflammatory phenotype. In vitro, salidroside suppressed the expression of pro-inflammatory cytokines and induced a switch in microglial phenotype to the anti-inflammatory phenotype. Mechanically, molecular docking studies revealed potential AMPK activation activity of salidroside. And salidroside did up-regulated the AMPK pathway proteins. Moreover, AMPK antagonist abolished the effects of salidroside in vivo and in vitro.Conclusions: Taken together, our results demonstrated that salidroside effectively suppressed PND by suppressing microglia-mediated neuroinflammation through activating AMPK pathway, and it might be a novel therapeutic approach for PND.

scholarly journals Wnt/β-catenin signaling regulates lipopolysaccharide-altered polarizations of RAW264.7 cells and alveolar macrophages in mouse lungs

2021 ◽  
Vol 19 ◽  
pp. 205873922110593
Author(s):  
Jiali Yang ◽  
Ying Wang ◽  
Dandan Yang ◽  
Jia Ma ◽  
Shuang Wu ◽  
...  
Keyword(s):  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Macrophage Polarization ◽  
Raw264.7 Cells ◽  
M1 Polarization ◽  
Inflammatory Phenotype ◽  
Inflammatory State ◽  
Anti Inflammatory

Introduction Macrophages are capable of exerting both proinflammatory and anti-inflammatory functions in response to distinct environmental stimuli, by polarizing into classically inflammatory state (M1) and anti-inflammatory phenotype (M2), respectively. The Wnt/β-catenin signaling plays an important role in the tissue homeostasis and immune regulations, including the macrophage polarizations. However, the molecular mechanism of Wnt/β-catenin signaling in regulating alveolar macrophage polarization in an inflammatory state remains unclear. Methods The Wnt/β-catenin signaling-altered phenotypes of murine macrophage-like RAW264.7 cells in vitro and alveolar macrophage in vivo in both of naïve and lipopolysaccharide-induced inflammation states were accessed by immunoblotting and immunostaining assays. Results The activation of Wnt/β-catenin signaling inhibited macrophage M1 polarization, but promoted alternative M2 polarization in murine RAW264.7 cells under a naïve state. Interestingly, in an LPS-induced inflammation condition, the enhanced Wnt/β-catenin activity suppressed both M1 and M2 polarizations in RAW264.7 cells in vitro, and primary alveolar macrophages of LPS-challenged mice in vivo. Molecular analysis further demonstrated an involvement of Stat signing in regulating Wnt/β-catenin signaling-altered polarizations in mouse alveolar macrophages. Conclusion These results suggest a mechanism by which Wnt/β-catenin signaling modulates macrophage polarization in an inflammation state by regulating the Stat signaling pathway.

scholarly journals β-Lactamase Production and Antimicrobial Susceptibility of Oral Heterogeneous Fusobacterium nucleatum Populations in Young Children

1999 ◽  
Vol 43 (5) ◽  
pp. 1270-1273 ◽  
Author(s):  
E. Könönen ◽  
A. Kanervo ◽  
K. Salminen ◽  
H. Jousimies-Somer
Keyword(s):  
Young Children ◽  
Clavulanic Acid ◽  
Antimicrobial Susceptibility ◽  
Fusobacterium Nucleatum ◽  
Penicillin G ◽  
Healthy Children ◽  
Good Activity ◽  
In Vitro Susceptibility ◽  
Amoxicillin Clavulanic Acid

ABSTRACT Oral Fusobacterium nucleatum populations from 20 young, healthy children were examined for β-lactamase production. Ten children (50%) harbored, altogether, 25 β-lactamase-positiveF. nucleatum isolates that were identified as F. nucleatum subsp. polymorphum, F. nucleatum subsp. nucleatum, and F. nucleatum subsp. vincentii (J. L. Dzink, M. T. Sheenan, and S. S. Socransky, Int. J. Syst. Bacteriol. 40:74–78, 1990). In vitro susceptibility of these β-lactamase-producing and 26 non-β-lactamase-producing F. nucleatum isolates was tested with penicillin G, amoxicillin-clavulanic acid, tetracycline hydrochloride, metronidazole, trovafloxacin, and azithromycin. Except for penicillin G, the antimicrobials exhibited good activity against all F. nucleatum isolates.

scholarly journals Central Nervous System Barriers Impact Distribution and Expression of iNOS and Arginase-1 in Infiltrating Macrophages During Neuroinflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniela C. Ivan ◽  
Sabrina Walthert ◽  
Giuseppe Locatelli
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Differential Distribution ◽  
General Ability ◽  
Border Regions ◽  
Arginase 1 ◽  
Tnf Α ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

In multiple sclerosis (MS) and other neuroinflammatory diseases, monocyte-derived cells (MoCs) traffic through distinct central nervous system (CNS) barriers and gain access to the organ parenchyma exerting detrimental or beneficial functions. How and where these MoCs acquire their different functional commitments during CNS invasion remains however unclear, thus hindering the design of MS treatments specifically blocking detrimental MoC actions. To clarify this issue, we investigated the distribution of iNOS+ pro-inflammatory and arginase-1+ anti-inflammatory MoCs at the distinct border regions of the CNS in a mouse model of MS. Interestingly, MoCs within perivascular parenchymal spaces displayed a predominant pro-inflammatory phenotype compared to MoCs accumulating at the leptomeninges and at the intraventricular choroid plexus (ChP). Furthermore, in an in vitro model, we could observe the general ability of functionally-polarized MoCs to migrate through the ChP epithelial barrier, together indicating the ChP as a potential CNS entry and polarization site for MoCs. Thus, pro- and anti-inflammatory MoCs differentially accumulate at distinct CNS barriers before reaching the parenchyma, but the mechanism for their phenotype acquisition remains undefined. Shedding light on this process, we observed that endothelial (BBB) and epithelial (ChP) CNS barrier cells can directly regulate transcription of Nos2 (coding for iNOS) and Arg1 (coding for arginase-1) in interacting MoCs. More specifically, while TNF-α+IFN-γ stimulated BBB cells induced Nos2 expression in MoCs, IL-1β driven activation of endothelial BBB cells led to a significant upregulation of Arg1 in MoCs. Supporting this latter finding, less pro-inflammatory MoCs could be found nearby IL1R1+ vessels in the mouse spinal cord upon neuroinflammation. Taken together, our data indicate differential distribution of pro- and anti-inflammatory MoCs at CNS borders and highlight how the interaction of MoCs with CNS barriers can significantly affect the functional activation of these CNS-invading MoCs during autoimmune inflammation.

scholarly journals A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV2 at the immune-epithelial interface

2021 ◽  
Author(s):  
Juliette Leon ◽  
Daniel A Michelson ◽  
Judith Olejnik ◽  
Kaitavjeet Chowdhary ◽  
Hyung Suk Oh ◽  
...  
Keyword(s):  
Influenza A ◽  
Ebola Virus ◽  
Multiorgan Failure ◽  
Healthy Children ◽  
Substantial Fraction ◽  
Strong Response ◽  
Mechanistic Insight ◽  
Inflammatory Phenotype ◽  
Transcriptional Induction

Infection by SARS-CoV2 provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight and ferret out the root of this immune dysregulation, we modeled by in vitro co-culture the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV2-specific inflammatory gene cluster distinct from that seen in influenza-A or Ebola virus-infected co-cultures, and which reproduced deviations reported in blood or lung myeloid cells from COVID-19 patients. A substantial fraction of the effect could be reproduced after individual transfection of several SARS-CoV2 proteins (Spike and some non-structural proteins), mediated by soluble factors, but not via transcriptional induction. This response was greatly muted in monocytes from healthy children, perhaps a clue to the age-dependency of COVID-19. These results suggest that the inflammatory malfunction in COVID-19 is rooted in the earliest perturbations that SARS-CoV2 induces in epithelia.

Sign in / Sign up

Export Citation Format

Share Document