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

2003 ◽  
Vol 284 (1) ◽  
pp. L108-L118 ◽  
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.

scholarly journals Therapeutic Role of miR-30a in Lipoteichoic Acid-Induced Endometritis via Targeting the MyD88/Nox2/ROS Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Kangfeng Jiang ◽  
Weiqi Ye ◽  
Qian Bai ◽  
Jinyin Cai ◽  
Haichong Wu ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Lipoteichoic Acid ◽  
In Vivo Studies ◽  
Economic Losses ◽  
Inflammatory Conditions ◽  
Wide Range

Staphylococcus aureus (S. aureus), a notorious pathogenic bacterium prevalent in the environment, causes a wide range of inflammatory diseases such as endometritis. Endometritis is an inflammatory disease in humans and mammals, which prolongs uterine involution and causes great economic losses. MiR-30a plays an importan trole in the process of inflammation; however, the regulatory role of miR-30a in endometritis is still unknown. Here, we first noticed that there was an increased level of miR-30a in uterine samples of cows with endometritis. And then, bovine endometrial epithelial (BEND) cells stimulated with the virulence factor lipoteichoic acid (LTA) from S. aureus were used as an in vitro endometritis model to explore the potential role of miR-30a in the pathogenesis of endometritis. Our data showed that the induction of the miR-30a expression is dependent on NF-κB activation, and its overexpression significantly decreased the levels of IL-1β and IL-6. Furthermore, we observed that the overexpression of miR-30a inhibited its translation by binding to 3 ′ − UTR of MyD88 mRNA, thus preventing the activation of Nox2 and NF-κB and ROS accumulation. Meanwhile, in vivo studies further revealed that upregulation of miR-30a using chemically synthesized agomirs alleviates the inflammatory conditions in an experimental mouse model of endometritis, as indicated by inhibition of ROS and NF-κB. Taken together, these findings highlight that miR-30a can attenuate LTA-elicited oxidative stress and inflammatory responses through the MyD88/Nox2/ROS/NF-κB pathway and may aid the future development of novel therapies for inflammatory diseases caused by S. aureus, including endometritis.

scholarly journals The Potential Neuroprotective Role of Free and Encapsulated Quercetin Mediated by miRNA against Neurological Diseases

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1318
Author(s):  
Tarek Benameur ◽  
Raffaella Soleti ◽  
Chiara Porro
Keyword(s):  
Inflammatory Responses ◽  
Pathological Condition ◽  
Neurological Diseases ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
In Vivo Studies ◽  
Innovative Drug ◽  
Chronic Neuroinflammation

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.

Phytochemistry and Pharmacology of the Genus Pedicularis Used in Traditional Chinese Medicine

2014 ◽  
Vol 42 (05) ◽  
pp. 1071-1098 ◽  
Author(s):  
Mao-Xing Li ◽  
Xi-Rui He ◽  
Rui Tao ◽  
Xinyuan Cao
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Chemical Constituents ◽  
Iridoid Glycosides ◽  
In Vivo Studies ◽  
Chemical Components ◽  
Wide Range ◽  
Phenylpropanoid Glycosides

In the present review, the literature data on the chemical constituents and biological investigations of the genus Pedicularis are summarized. Some species of Pedicularis have been widely applied in traditional Chinese medicine. A wide range of chemical components including iridoid glycosides, phenylpropanoid glycosides (PhGs), lignans glycosides, flavonoids, alkaloids and other compounds have been isolated and identified from the genus Pedicularis. In vitro and in vivo studies indicated some monomer compounds and extracts from the genus Pedicularis have been found to possess antitumor, hepatoprotective, anti-oxidative, antihaemolysis, antibacterial activity, fatigue relief of skeletal muscle, nootropic effect and other activities.

scholarly journals Selective induction of endothelial P2Y6 nucleotide receptor promotes vascular inflammation

Blood ◽  
2011 ◽  
Vol 117 (8) ◽  
pp. 2548-2555 ◽  
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.

scholarly journals Development of an LDL Receptor-Targeted Peptide Susceptible to Facilitate the Brain Access of Diagnostic or Therapeutic Agents

Biology ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 161
Author(s):  
Séverine André ◽  
Lionel Larbanoix ◽  
Sébastien Verteneuil ◽  
Dimitri Stanicki ◽  
Denis Nonclercq ◽  
...  
Keyword(s):  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Therapeutic Agents ◽  
In Vivo Studies ◽  
Phage Display Technology ◽  
Brain Penetration ◽  
Wide Range ◽  
The Brain

Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed, and a wide range of approaches (invasive or not) have been proposed so far. The receptor-mediated transcytosis is an attractive mechanism, allowing the non-invasive penetration of the BBB. Among available targets, the low-density lipoprotein (LDL) receptor (LDLR) shows favorable characteristics mainly because of the lysosome-bypassed pathway of LDL delivery to the brain, allowing an intact discharge of the carried ligand to the brain targets. The phage display technology was employed to identify a dodecapeptide targeted to the extracellular domain of LDLR (ED-LDLR). This peptide was able to bind the ED-LDLR in the presence of natural ligands and dissociated at acidic pH and in the absence of calcium, in a similar manner as the LDL. In vitro, our peptide was endocytosed by endothelial cells through the caveolae-dependent pathway, proper to the LDLR route in BBB, suggesting the prevention of its lysosomal degradation. The in vivo studies performed by magnetic resonance imaging and fluorescent lifetime imaging suggested the brain penetration of this ED-LDLR-targeted peptide.

scholarly journals Safety and Utility of Chloroquine/ Hydroxychloroquine in Palliative Care Patients

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.

scholarly journals Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1232
Author(s):  
Stefania D’Adamo ◽  
Silvia Cetrullo ◽  
Veronica Panichi ◽  
Erminia Mariani ◽  
Flavio Flamigni ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Antioxidant Activities ◽  
Synergistic Effects ◽  
National Health System ◽  
Bioactive Molecules ◽  
Joint Disease ◽  
In Vivo Studies ◽  
Wide Range

Osteoarthritis (OA) is a disease associated to age or conditions that precipitate aging of articular cartilage, a post-mitotic tissue that remains functional until the failure of major homeostatic mechanisms. OA severely impacts the national health system costs and patients’ quality of life because of pain and disability. It is a whole-joint disease sustained by inflammatory and oxidative signaling pathways and marked epigenetic changes responsible for catabolism of the cartilage extracellular matrix. OA usually progresses until its severity requires joint arthroplasty. To delay this progression and to improve symptoms, a wide range of naturally derived compounds have been proposed and are summarized in this review. Preclinical in vitro and in vivo studies have provided proof of principle that many of these nutraceuticals are able to exert pleiotropic and synergistic effects and effectively counteract OA pathogenesis by exerting both anti-inflammatory and antioxidant activities and by tuning major OA-related signaling pathways. The latter are the basis for the nutrigenomic role played by some of these compounds, given the marked changes in the transcriptome, miRNome, and methylome. Ongoing and future clinical trials will hopefully confirm the disease-modifying ability of these bioactive molecules in OA patients.

scholarly journals Pleiotropic Biological Effects of Dietary Phenolic Compounds and their Metabolites on Energy Metabolism, Inflammation and Aging

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 596 ◽  
Author(s):  
María del Carmen Villegas-Aguilar ◽  
Álvaro Fernández-Ochoa ◽  
María de la Luz Cádiz-Gurrea ◽  
Sandra Pimentel-Moral ◽  
Jesús Lozano-Sánchez ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Phenolic Compounds ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Biological Properties ◽  
In Vivo Studies ◽  
Wide Range ◽  
High Prevalence

Dietary phenolic compounds are considered as bioactive compounds that have effects in different chronic disorders related to oxidative stress, inflammation process, or aging. These compounds, coming from a wide range of natural sources, have shown a pleiotropic behavior on key proteins that act as regulators. In this sense, this review aims to compile information on the effect exerted by the phenolic compounds and their metabolites on the main metabolic pathways involved in energy metabolism, inflammatory response, aging and their relationship with the biological properties reported in high prevalence chronic diseases. Numerous in vitro and in vivo studies have demonstrated their pleiotropic molecular mechanisms of action and these findings raise the possibility that phenolic compounds have a wide variety of roles in different targets.

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

2009 ◽  
Vol 6 (1) ◽  
pp. 34 ◽  
Author(s):  
Ingrid Beck-Speier ◽  
Wolfgang G Kreyling ◽  
Konrad L Maier ◽  
Niru Dayal ◽  
Mette C Schladweiler ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Prostaglandin E2 ◽  
Inflammatory Responses ◽  
Oxide Particle ◽  
In Vivo Studies ◽  
Iron Oxide Particle ◽  
Soluble Iron

scholarly journals Synergistic interactions between interferon-γ and TRAIL modulate c-FLIP in endothelial cells, mediating their lineage-specific sensitivity to thrombotic thrombocytopenic purpura plasma–associated apoptosis

Blood ◽  
2008 ◽  
Vol 112 (2) ◽  
pp. 340-349 ◽  
Author(s):  
Radu Stefanescu ◽  
Dustin Bassett ◽  
Rozbeh Modarresi ◽  
Francisco Santiago ◽  
Mohamad Fakruddin ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Interferon Γ ◽  
Microvascular Endothelial Cell ◽  
Caspase 8 ◽  
Inhibitory Protein ◽  
Thrombocytopenic Purpura ◽  
Ifn Γ ◽  
Interfering Rna

Abstract Microvascular endothelial cell (MVEC) injury coupled to progression of platelet microthrombi facilitated by ADAMTS13 deficiency is characteristic of idiopathic and HIV-linked thrombotic thrombocytopenic purpura (TTP). Cytokines capable of inducing MVEC apoptosis in vitro are up-regulated in both TTP and HIV infection. However, the concentrations of these cytokines required to elicit EC apoptosis in vitro are 2- to 3-log–fold greater than present in patient plasmas. We report that clinically relevant levels of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and interferon (IFN)–γ act in synergy to induce apoptosis in dermal MVECs, but have no effect on large-vessel ECs or pulmonary MVECs. This reflects the tissue distribution of TTP lesions in vivo. Sensitivity to TTP plasma or TRAIL plus IFN-γ is paralleled by enhanced ubiquitination of the caspase-8 regulator cellular FLICE-like inhibitory protein (c-FLIP), targeting it for proteasome degradation. c-FLIP silencing with anti-FLIP short interfering RNA (siRNA) in pulmonary MVECs rendered them susceptible to TTP plasma– and cytokine-mediated apoptosis, while up-regulation of c-FLIP by gene transfer partially protected dermal MVECs from such injury. TTP plasma–mediated apoptosis appears to involve cytokine-induced acceleration of c-FLIP degradation, sensitizing cells to TRAIL-mediated caspase-8 activation and cell death. Suppression of TRAIL or modulation of immunoproteasome activity may have therapeutic relevance in TTP.

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