Soluble iron modulates iron oxide particle-induced inflammatory responses via prostaglandin E2 synthesis: In vitro and in vivo studies

Chronic neuroinflammation is a pathological condition of numerous central nervous system (CNS) diseases such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis and many others. Neuroinflammation is characterized by the microglia activation and concomitant production of pro-inflammatory cytokines leading to an increasing neuronal cell death. The decreased neuroinflammation could be obtained by using natural compounds, including flavonoids known to modulate the inflammatory responses. Among flavonoids, quercetin possess multiple pharmacological applications including anti-inflammatory, antitumoral, antiapoptotic and anti-thrombotic activities, widely demonstrated in both in vitro and in vivo studies. In this review, we describe the recent findings about the neuroprotective action of quercetin by acting with different mechanisms on the microglial cells of CNS. The ability of quercetin to influence microRNA expression represents an interesting skill in the regulation of inflammation, differentiation, proliferation, apoptosis and immune responses. Moreover, in order to enhance quercetin bioavailability and capacity to target the brain, we discuss an innovative drug delivery system. In summary, this review highlighted an important application of quercetin in the modulation of neuroinflammation and prevention of neurological disorders.

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Selective induction of endothelial P2Y6 nucleotide receptor promotes vascular inflammation

Blood ◽

10.1182/blood-2010-10-313957 ◽

2011 ◽

Vol 117 (8) ◽

pp. 2548-2555 ◽

Cited By ~ 78

Author(s):

Ann-Kathrin Riegel ◽

Marion Faigle ◽

Stephanie Zug ◽

Peter Rosenberger ◽

Bernard Robaye ◽

...

Keyword(s):

Inflammatory Responses ◽

Vascular Inflammation ◽

In Vivo Studies ◽

Nucleotide Receptors ◽

Transcriptional Responses ◽

Lps Challenge ◽

Screening Experiments ◽

P2y6 Receptor

Abstract During a systemic inflammatory response endothelial-expressed surface molecules have been strongly implicated in orchestrating immune responses. Previous studies have shown enhanced extracellular nucleotide release during acute inflammatory conditions. Therefore, we hypothesized that endothelial nucleotide receptors could play a role in vascular inflammation. To address this hypothesis, we performed screening experiments and exposed human microvascular endothelia to inflammatory stimuli, followed by measurements of P2Y or P2X transcriptional responses. These studies showed a selective induction of the P2Y6 receptor (> 4-fold at 24 hours). Moreover, studies that used real-time reverse transcription–polymerase chain reaction, Western blot analysis, or immunofluorescence confirmed time- and dose-dependent induction of P2Y6 with tumor necrosis factor α or Lipopolysaccharide (LPS) stimulation in vitro and in vivo. Studies that used MRS 2578 as P2Y6 receptor antagonist showed attenuated nuclear factor κB reporter activity and proinflammatory gene expression in human microvascular endothelial cells in vitro. Moreover, pharmacologic or genetic in vivo studies showed attenuated inflammatory responses in P2Y6−/− mice or after P2Y6 antagonist treatment during LPS-induced vascular inflammation. These studies show an important contribution of P2Y6 signaling in enhancing vascular inflammation during systemic LPS challenge and implicate the P2Y6 receptor as a therapeutic target during systemic inflammatory responses.

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Safety and Utility of Chloroquine/ Hydroxychloroquine in Palliative Care Patients

American Journal of Hospice and Palliative Medicine® ◽

10.1177/1049909120952773 ◽

2020 ◽

pp. 104990912095277

Author(s):

Eric Prommer

Keyword(s):

Palliative Care ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Symptom Control ◽

In Vivo Studies ◽

Advanced Illness ◽

Know How ◽

Seriously Ill

The coronavirus disease 2019 (COVID-19) pandemic represents a significant healthcare challenge for the world. Many drugs have therapeutic potential. The aminoquinolones, hydroxychloroquine, and chloroquine are undergoing evaluation as a potential therapy against COVID -19. In vitro and in vivo studies suggest that these drugs affect viral adherence and modify inflammatory responses, which may provide some impact on the symptoms associated with COVID. As palliative care specialists encounter more COVID positive patients, palliative care specialists need to know how these drugs work, and importantly how they interact with palliative care drugs used for symptom control. At the same time, there is a need to reduce polypharmacy in any seriously ill patient population. The goals of this paper are to identify whether or not hydroxychloroquine/chloroquine improves symptoms in palliative care patients and whether or not these drugs are safe to use in the advanced illness population who have COVID.

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Enhanced In Vitro and In Vivo Cellular Imaging with Green Tea Coated Water-Soluble Iron Oxide Nanocrystals

ACS Applied Materials & Interfaces ◽

10.1021/am508404t ◽

2015 ◽

Vol 7 (12) ◽

pp. 6530-6540 ◽

Cited By ~ 38

Author(s):

Lisong Xiao ◽

Marianne Mertens ◽

Laura Wortmann ◽

Silke Kremer ◽

Martin Valldor ◽

...

Keyword(s):

Iron Oxide ◽

Green Tea ◽

Cellular Imaging ◽

Water Soluble ◽

Soluble Iron

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Carpesium macrocephalum Attenuates Lipopolysaccharide-Induced Inflammation in Macrophages by Regulating the NF-κB/IκB-α, Akt, and STAT Signaling Pathways

The American Journal of Chinese Medicine ◽

10.1142/s0192415x13500626 ◽

2013 ◽

Vol 41 (04) ◽

pp. 927-943 ◽

Cited By ~ 17

Author(s):

Sushruta Koppula ◽

Wan-Jae Kim ◽

Jun Jiang ◽

Do-Wan Shim ◽

Na-Hyun Oh ◽

...

Keyword(s):

Inflammatory Responses ◽

In Vivo Studies ◽

Raw264.7 Cells ◽

Traditional Use ◽

Necrosis Factor Alpha ◽

Proinflammatory Mediators ◽

Raw264.7 Macrophages ◽

Anti Inflammatory

Carpesium macrocephalum (CM) Fr. et Sav. (Compositae) has been used in Chinese folk medicine as an analgesic, hemostatic, antipyretic, and to suppress inflammatory conditions. In the present study we aimed to provide scientific evidence for the anti-inflammatory properties of CM extract and evaluate the intrinsic mechanisms involved in both in vitro and in vivo experimental models. In in vitro findings, CM significantly inhibited the LPS-stimulated release of proinflammatory mediators such as nitric oxide, tumor necrosis factor-alpha, prostaglandin E2, and interleukin-6 in RAW264.7 macrophages in a concentration-dependent fashion. The attenuation of inflammatory responses in LPS-activated RAW264.7 cells by CM was closely associated with the suppression of nuclear factor-kappa B (NF-κB) phosphorylation, IκB-α degradation, and phosphorylation of Akt. CM treatment also attenuated the phosphorylation of STAT through TRIF dependent pathways in LPS-activated RAW264.7 cells. In vivo studies revealed that CM extract concentration dependently suppressed the acetic acid-induced vascular permeability in mice. Considering the data obtained regulation of multiple signaling mechanisms involving TRIF and Akt/NF-κB pathways might be responsible for the potent anti-inflammatory action of CM, substantiating its traditional use in inflammatory diseases.

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Transcriptional regulation of CCSP by interferon-γ in vitro and in vivo

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00186.2002 ◽

2003 ◽

Vol 284 (1) ◽

pp. L108-L118 ◽

Cited By ~ 13

Author(s):

P. L. Ramsay ◽

Z. Luo ◽

S. M. Magdaleno ◽

S. K. Whitbourne ◽

X. Cao ◽

...

Keyword(s):

Inflammatory Responses ◽

Interferon Γ ◽

Clara Cell ◽

In Vivo Studies ◽

Deletion Mapping ◽

Induced Expression ◽

Wide Range ◽

Ifn Γ

Interferon γ (IFN-γ), a potent cytokine inducing a wide range of immunologic activities, is increased in the airway secondary to viral infection or during an inflammatory response. This increase in IFN-γ concentration may alter the expression of specific airway epithelial cell genes that regulate adaptation of airway inflammatory responses. One protein induced by IFN-γ is Clara cell secretory protein (CCSP), which may contribute to the attenuation of airway inflammation. This study was done to investigate the molecular mechanism by which IFN-γ stimulates the expression of the CCSP gene in mouse transformed Clara cells and transgenic mice. Deletion mapping and linker-scanning mutations demonstrated that IFN-γ-induced expression of CCSP was regulated, in part, at the level of transcription. In vitro and in vivo studies verified that the minimal IFN-γ-responsive segment was localized to the proximal 166 bp of the 5′-flanking region. Additionally, IFN-γ-induced expression of CCSP was mediated indirectly through an interferon regulatory factor-1-mediated increase in hepatocyte nuclear factor-3β.

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The Impact of Acute or Chronic Alcohol Intake on the NF-κB Signaling Pathway in Alcohol-Related Liver Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21249407 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9407

Author(s):

Aleksander J. Nowak ◽

Borna Relja

Keyword(s):

Liver Disease ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Current Knowledge ◽

In Vivo Studies ◽

Related Liver Disease ◽

The Impact

Ethanol misuse is frequently associated with a multitude of profound medical conditions, contributing to health-, individual- and social-related damage. A particularly dangerous threat from this classification is coined as alcoholic liver disease (ALD), a liver condition caused by prolonged alcohol overconsumption, involving several pathological stages induced by alcohol metabolic byproducts and sustained cellular intoxication. Molecular, pathological mechanisms of ALD principally root in the innate immunity system and are especially associated with enhanced functionality of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. NF-κB is an interesting and convoluted DNA transcription regulator, promoting both anti-inflammatory and pro-inflammatory gene expression. Thus, the abundancy of studies in recent years underlines the importance of NF-κB in inflammatory responses and the mechanistic stimulation of inner molecular motifs within the factor components. Hereby, in the following review, we would like to put emphasis on the correlation between the NF-κB inflammation signaling pathway and ALD progression. We will provide the reader with the current knowledge regarding the chronic and acute alcohol consumption patterns, the molecular mechanisms of ALD development, the involvement of the NF-κB pathway and its enzymatic regulators. Therefore, we review various experimental in vitro and in vivo studies regarding the research on ALD, including the recent active compound treatments and the genetic modification approach. Furthermore, our investigation covers a few human studies.

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LPS Induces Opposing Memory-like Inflammatory Responses in Mouse Bone Marrow Neutrophils

International Journal of Molecular Sciences ◽

10.3390/ijms22189803 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9803

Author(s):

Trim Lajqi ◽

Maylis Braun ◽

Simon Alexander Kranig ◽

David Frommhold ◽

Johannes Pöschl ◽

...

Keyword(s):

Bone Marrow ◽

Immune Cells ◽

Inflammatory Responses ◽

Innate Immune ◽

In Vivo Studies ◽

Mouse Bone Marrow ◽

Innate Immune Cells ◽

Trained Immunity

A growing body of evidence suggests that innate immune cells can respond in a memory-like (adaptive) fashion, which is referred to as trained immunity. Only few in vivo studies have shown training effects in neutrophils; however, no in vitro setup has been established to study the induction of trained immunity or tolerance in neutrophils by microbial agents. In light of their short lifespan (up to 48 h), we suggest to use the term trained sensitivity for neutrophils in an in vitro setting. Here, we firstly describe a feasible two-hit model, using different doses of lipopolysaccharide (LPS) in bone marrow neutrophils. We found that low doses (10 pg/mL) induce pro-inflammatory activation (trained sensitivity), whereas priming with high doses (100 ng/mL) leads to suppression of pro-inflammatory mediators such as TNF-α or IL-6 (tolerance) (p < 0.05). On a functional level, trained neutrophils displayed increased phagocytic activity and LFA-1 expression as well as migrational capacity and CD11a expression, whereas tolerant neutrophils show contrasting effects in vitro. Mechanistically, TLR4/MyD88/PI3Ks regulate the activation of p65, which controls memory-like responses in mouse bone marrow neutrophils (p < 0.05). Our results open a new window for further in vitro studies on memory-like inflammatory responses of short-lived innate immune cells such as neutrophils.

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Vitamin D3 Controls TLR4- and TLR2-Mediated Inflammatory Responses of Endometrial Cells

Gynecologic and Obstetric Investigation ◽

10.1159/000513590 ◽

2021 ◽

pp. 1-10

Author(s):

Alireza Ghanavatinejad ◽

Nesa Rashidi ◽

Mahroo Mirahmadian ◽

Simin Rezania ◽

Mahdokht Mosalaei ◽

...

Keyword(s):

Reproductive Tract ◽

Inflammatory Responses ◽

Female Reproductive Tract ◽

In Vivo Studies ◽

Endometrial Stromal Cells ◽

Endometrial Cells ◽

Tnf Α ◽

Tract Infections

Objectives: Vitamin D has potent immunoregulatory features and modulates innate and adaptive immune responses. There is a significant association between intrauterine infection-associated inflammatory responses and pregnancy complications such as abortion and preterm labor. Here, we investigated how 1,25 (OH)2 D3 could modulate inflammatory responses of endometrial cells. Design: This is an in vitro experimental study. Endometrial stromal cells (ESCs) and whole endometrial cells (WECs) were collected from 15 apparently normal women, and the immunomodulatory effects of 1,25 (OH)2 D3 on lipopolysaccharide (LPS)- or lipoteichoic acid (LTA)-treated ESCs and WECs were investigated. Participants/Materials, Setting, and Methods: Women with no history of abortion, infertility, endometriosis, or sign of vaginal infection were enrolled in this study. Endometrial samples were collected by gynecologists using a Pipelle pipette in the proliferative phase of the menstrual cycle. WECs and ESCs were collected and treated with either LPS or LTA. The levels of IL-6, IL-8, and TNF-α in culture supernatants were quantified using the ELISA technique. TLR2, TLR4, and MyD88 expressions were assessed by RT-qPCR. TLR4 expression at the protein level was studied by the Western blot technique. Results: 1,25 Dihydroxycholecalciferol (1,25 (OH)2 D3) significantly reduced TNF-α production in LPS-activated ESCs and TNF-α and IL-6 production by LTA-stimulated WECs. In contrast, 1,25 (OH)2 D3 pretreatment increased the production of IL-8 by LPS- and LTA-stimulated endometrial cells. 1,25 (OH)2 D3 pretreatment markedly reduced LPS-induced TLR4 protein expression by ESCs. LPS treatment of ESCs significantly induced MyD88 gene expression. This effect was reversed when these cells were pretreated with 1,25 (OH)2 D3 before stimulation with LPS. Limitations: Because of the small size of samples, doing experiments all together on some samples was not feasible. Confirmation of the results obtained here needs well-designed in vivo studies. Conclusions: 1,25 (OH)2 D3 is an immunomodulatory molecule essential for maintaining endometrial immune homeostasis by controlling potentially harmful inflammatory responses associated with female reproductive tract infections.

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