Selective induction of phospholipase D1 in pathogen-activated human monocytes

2001 ◽  
Vol 358 (1) ◽  
pp. 119-125 ◽  
Author(s):  
Massimo LOCATI ◽  
Elena RIBOLDI ◽  
Raffaella BONECCHI ◽  
Pietro TRANSIDICO ◽  
Sergio BERNASCONI ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Cell Activation ◽  
Interferon Γ ◽  
Culture Conditions ◽  
Enzymic Activity ◽  
Human Monocytes ◽  
Protein Levels ◽  
Phospholipase D1 ◽  
Inducible Protein ◽  
Factor Α

Phospholipase D (PLD) activation is part of the complex signalling cascade induced during phagocyte activation. Two PLD isoforms have been cloned, but their role in phagocyte functions is still poorly defined. We report that resting fresh circulating human monocytes expressed PLD1. PLD1 protein expression was rapidly down-regulated during cell culture. Lipopolysaccharide and pathogen-derived agonists (Candida albicans, arabinoside-terminated lipoarabinomannan and Gram-positive bacteria, but not mannose-capped lipoarabinomannan or double-stranded RNA) strongly induced PLD1 expression at both the mRNA and protein levels. Pro-inflammatory cytokines [interleukin (IL)-1β and tumour necrosis factor α] had only a weak effect, whereas immune cytokines (IL-6 and interferon γ), anti-inflammatory cytokines (IL-13 and IL-10) and chemoattractants (fMet-Leu-Phe and macrophage chemoattractant protein 1) were inactive. None of the agonists tested induced significant changes in the basal expression of PLD2 mRNA. Consistent with PLD1 up-regulation was the observation that PLD enzymic activity was higher in monocytes treated with active-pathogen-derived agonists than in control cells, when stimulated with PMA or with chemotactic agonists (fMet-Leu-Phe and C5a). Thus PLD2 seems to be a constitutive enzyme in circulating monocytes. Conversely, PLD1 is an inducible protein, rapidly regulated during culture conditions and selectively induced during cell activation. Therefore PLD1 might have a relevant role in immune responses against pathogens and in chronic inflammation.

scholarly journals HIF1α/TET1 Pathway Mediates Hypoxia-Induced Adipocytokine Promoter Hypomethylation in Human Adipocytes

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 134 ◽  
Author(s):  
Mohamed M. Ali ◽  
Shane A. Phillips ◽  
Abeer M. Mahmoud
Keyword(s):  
Dna Methylation ◽  
Interleukin 1 ◽  
Hypoxia Inducible Factor ◽  
Interferon Γ ◽  
The Body ◽  
Human Adipocytes ◽  
Protein Levels ◽  
Factor Α ◽  
Necrosis Factor

Obesity is associated with the accumulation of dysfunctional adipose tissue that secretes several pro-inflammatory cytokines (adipocytokines). Recent studies have presented evidence that adipose tissues in obese individuals and animal models are hypoxic, which may result in upregulation and stabilization of the hypoxia inducible factor HIF1α. Epigenetic mechanisms such as DNA methylation enable the body to respond to microenvironmental changes such as hypoxia and may represent a mechanistic link between obesity-associated hypoxia and upregulated inflammatory adipocytokines. The purpose of this study was to investigate the role of hypoxia in modifying adipocytokine DNA methylation and subsequently adipocytokine expression. We suggested that this mechanism is mediated via the DNA demethylase, ten-eleven translocation-1 (TET1), transcription of which has been shown to be induced by HIF1α. To this end, we studied the effect of hypoxia (2% O2) in differentiated subcutaneous human adipocytes in the presence or absence of HIF1α stabilizer (Dimethyloxalylglycine (DMOG), 500 μM), HIF1α inhibitor (methyl 3-[[2-[4-(2-adamantyl) phenoxy] acetyl] amino]-4-hydroxybenzoate, 30 μM), or TET1-specific siRNA. Subjecting the adipocytes to hypoxia significantly induced HIF1α and TET1 protein levels. Moreover, hypoxia induced global hydroxymethylation, reduced adipocytokine DNA promoter methylation, and induced adipocytokine expression. These effects were abolished by either HIF1α inhibitor or TET1 gene silencing. The major hypoxia-responsive adipocytokines were leptin, interleukin-1 (IL6), IL1β, tumor necrosis factor α (TNFα), and interferon γ (IFNγ). Overall, these data demonstrate an activation of the hydroxymethylation pathway mediated by TET1. This pathway contributes to promoter hypomethylation and gene upregulation of the inflammatory adipocytokines in adipocytes in response to hypoxia.

scholarly journals Antidepressant-Like Effect and Mechanism of Action of Honokiol on the Mouse Lipopolysaccharide (LPS) Depression Model

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2035 ◽  
Author(s):  
Bo Zhang ◽  
Ping-Ping Wang ◽  
Kai-Li Hu ◽  
Li-Na Li ◽  
Xue Yu ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Mechanism Of Action ◽  
Tail Suspension Test ◽  
Interferon Γ ◽  
Biologically Active ◽  
Free Calcium ◽  
Immobility Time ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Pro Inflammatory Cytokines

There is growing evidence that neuroinflammation is closely linked to depression. Honokiol, a biologically active substance extracted from Magnolia officinalis, which is widely used in traditional Chinese medicine, has been shown to exert significant anti-inflammatory effects and improve depression-like behavior caused by inflammation. However, the specific mechanism of action of this activity is still unclear. In this study, the lipopolysaccharide (LPS) mouse model was used to study the effect of honokiol on depression-like behavior induced by LPS in mice and its potential mechanism. A single administration of LPS (1 mg/kg, intraperitoneal injection) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), without affecting autonomous activity. Pretreatment with honokiol (10 mg/kg, oral administration) for 11 consecutive days significantly improved the immobility time of depressed mice in the FST and TST experiments. Moreover, honokiol ameliorated LPS-induced NF-κB activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). In addition, honokiol inhibited LPS-induced indoleamine 2,3-dioxygenase (IDO) activation and quinolinic acid (a toxic product) increase and reduced the level of free calcium in brain tissue, thereby inhibiting calcium overload. In summary, our results indicate that the anti-depressant-like effects of honokiol are mediated by its anti-inflammatory effects. Honokiol may inhibit the LPS-induced neuroinflammatory response through the NF-κB signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.

In situ profiling of adipokines in subcutaneous microdialysates from lean and obese individuals

2008 ◽  
Vol 295 (5) ◽  
pp. E1095-E1105 ◽  
Author(s):  
Giuseppe Murdolo ◽  
Christian Herder ◽  
Zhaohui Wang ◽  
Bettina Rose ◽  
Martin Schmelz ◽  
...  
Keyword(s):  
Time Frame ◽  
Interferon Γ ◽  
Optimal Time ◽  
Serum Concentrations ◽  
Time Pattern ◽  
Monocyte Chemoattractant Protein 1 ◽  
Inducible Protein ◽  
Factor Α ◽  
Probe Insertion

Adipose tissue (AT) had emerged as an endocrine organ and a key regulator of the metabolically triggered inflammation. The aims of this study were 1) to investigate the usefulness of a multiplexed bioassay in characterizing a panel of adipokines in subcutaneous (sc) microdialysate samples and 2) to determine whether lean and obese individuals differ in their interstitial adipokines levels following microdialysis (MD) probe insertion. Ultrafiltrating MD membranes were inserted in opposite sites of the sc abdominal AT of six lean (L) and six obese (OB) males at the beginning (M1) and during the last 120 min (M2) of the study. Interstitial and serum concentrations of adipokines were quantified using the Luminex technique and ELISA at 60-min intervals for 5 h. In comparison with L subjects, OB subjects exhibited elevated interstitial leptin ( P < 0.001), IL-8 ( P < 0.05), and IL-18 levels ( P = 0.05), as well as higher serum concentrations of leptin ( P < 0.0001), IL-6 ( P < 0.0001), tumor necrosis factor-α ( P < 0.001), IL-8 ( P = 0.01) and interferon-γ-inducible protein 10 ( P < 0.05). In samples from the M1 membranes, leptin decreased and IL-1α, IL-18, and RANTES (regulated on activation, normal T-cell expressed and secreted) remained relatively stable, whereas IL-6, IL-8, and monocyte chemoattractant protein-1 significantly increased after the first hour ( P < 0.0001 vs. baseline). Notably, either the magnitude of increase from the initial values or the time pattern of all the adipokines in M1 and M2 dialysates were similar between the groups. In conclusion, the current work provides valuable information on the optimal time frame to collect in situ AT microdialysate samples. Further studies are needed, however, to unravel the intricate interplay of cytokines in AT interstitial fluid.

scholarly journals Comorbidities and inflammation associated with ovarian cancer and its influence on SARS-CoV-2 infection

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sima Chaudhari ◽  
Satyajit Dey Pereira ◽  
Meshach Asare-Warehene ◽  
Ritam Naha ◽  
Shama Prasada Kabekkodu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Stage ◽  
Interferon Γ ◽  
Health Concern ◽  
Colony Stimulating Factor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Cytokines And Chemokines ◽  
Inducible Protein ◽  
Factor Α ◽  
Stimulating Factor

AbstractCoronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide is a major public health concern. Cancer patients are considered a vulnerable population to SARS-CoV-2 infection and may develop several COVID-19 symptoms. The heightened immunocompromised state, prolonged chronic pro-inflammatory milieu coupled with comorbid conditions are shared in both disease conditions and may influence patient outcome. Although ovarian cancer (OC) and COVID-19 are diseases of entirely different primary organs, both diseases share similar molecular and cellular characteristics in their microenvironment suggesting a potential cooperativity leading to poor outcome. In COVID-19 related cases, hospitalizations and deaths worldwide are lower in women than in males; however, comorbidities associated with OC may increase the COVID-19 risk in women. The women at the age of 50-60 years are at greater risk of developing OC as well as SARS-CoV-2 infection. Increased levels of gonadotropin and androgen, dysregulated renin-angiotensin-aldosterone system (RAAS), hyper-coagulation and chronic inflammation are common conditions observed among OC and severe cases of COVID-19. The upregulation of common inflammatory cytokines and chemokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-2, IL-6, IL-10, interferon-γ-inducible protein 10 (IP-10), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), among others in the sera of COVID-19 and OC subjects suggests potentially similar mechanism(s) involved in the hyper-inflammatory condition observed in both disease states. Thus, it is conceivable that the pathogenesis of OC may significantly contribute to the potential infection by SARS-CoV-2. Our understanding of the influence and mechanisms of SARS-CoV-2 infection on OC is at an early stage and in this article, we review the underlying pathogenesis presented by various comorbidities of OC and correlate their influence on SARS-CoV-2 infection.

The Impact of Physical Activity on Serum Inflammatory Markers in Overweight Pubertal Boys: 24-Month Follow-Up Study

2018 ◽  
Vol 30 (2) ◽  
pp. 198-207
Author(s):  
Liina Remmel ◽  
Vallo Tillmann ◽  
Eva Mengel ◽  
Pille Kool ◽  
Priit Purge ◽  
...  
Keyword(s):  
Physical Activity ◽  
Growth Factor ◽  
Inflammatory Cytokines ◽  
Inflammatory Markers ◽  
Vigorous Physical Activity ◽  
Interferon Γ ◽  
Active Group ◽  
Chemotactic Protein ◽  
Factor Α ◽  
The Impact

Purpose: To investigate the differences in the pattern of changes in serum inflammatory cytokines measured annually over a 24-month period, between less active and more active overweight boys. Participants/Methods: In total, 25 pubertal overweight boys were divided by their moderate to vigorous physical activity (MVPA) levels into 2 groups: less active group (LAG; n = 10; MVPA < 60 min/d) and more active group (MAG; n = 15; MVPA > 60 min/d). Physical activity was measured by 7-day accelerometry. Serum concentration of 13 inflammatory cytokines [interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, vascular endothelial growth factor, interferon-γ, tumor necrosis factor-α, monocyte chemotactic protein-1, epidermal growth factor, and C-reactive protein] was measured at baseline (T0), after 12 months (T1), and after 24 months (T2) from fasting blood samples. Results: Serum IL-6 level was significantly higher [LAG: 1.27 (0.86, 1.98) pg/mL; MAG: 0.80 (0.52, 0.84) pg/mL] at T0 and IL-8 level [LAG: 10.26 (8.80, 11.64) pg/mL; MAG: 7.42 (6.10, 9.54) pg/mL] at T2 in LAG compared with MAG. The changes over the study period varied between different inflammatory markers. None of the slopes of any measured markers were statistically different between the LAG and MAG, although the slopes of interferon-γ and IL-10 tended to be different between the groups. Conclusions: The pattern of changes over the study period varied between different inflammatory markers, but these changes were not different between the MVPA groups. More longitudinal studies are needed to investigate whether IL-6, IL-8, IL-10, and interferon-γ would be the choice of inflammatory markers to study the associations between obesity and physical activity in future.

scholarly journals Enhanced Immune Response by Vacuoles isolated from Saccharomyces cerevisiae in RAW 264.7 Macrophages

2021 ◽  
Author(s):  
Su-Min Lee ◽  
Wooil Choi ◽  
Woo-Ri Shin ◽  
Yang-Hoon Kim ◽  
Jiho Min
Keyword(s):  
Nitric Oxide ◽  
Immune Response ◽  
Inflammatory Cytokines ◽  
Membrane Vesicles ◽  
No Production ◽  
Macrophage Activity ◽  
Protein Levels ◽  
Immune Mediated ◽  
Factor Α ◽  
Pro Inflammatory Cytokines

Vacuoles are membrane vesicles in eukaryotic cells, the digestive system of cells that break down substances absorbed outside the cell and digest the useless components of the cell itself. Researches on anti-cancer and intractable diseases using vacuoles are being actively conducted. The practical application of this study to animals requires the determination of the biocompatibility of vacuole. In the present study, we evaluated the effects of vacuoles isolated from S. cerevisiae in RAW264.7 cells. This showed a significant increase in the production of nitric oxide produced by macrophage activity. Using Reactive Oxygen Species (ROS) Assay, we identified that ROS is increased in a manner dependent on vacuole concentration. Western blot analysis showed that vacuole concentration-dependently increased protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2). Therefore, iNOS expression was stimulated to induce Nitric oxide (NO) production. In addition, pro-inflammatory cytokines levels promoted, such as interleukin 6 and tumor necrosis factor -α. In summary, vacuoles activate the immune response of macrophages by promoting the production of immune-mediated transporters NO, ROS, and pro-inflammatory cytokines.

scholarly journals Cd40 Ligand (Cd154) Triggers a Short-Term Cd4+ T Cell Activation Response That Results in Secretion of Immunomodulatory Cytokines and Apoptosis

2000 ◽  
Vol 191 (4) ◽  
pp. 651-660 ◽  
Author(s):  
Patrick J. Blair ◽  
James L. Riley ◽  
David M. Harlan ◽  
Ryo Abe ◽  
Douglas K. Tadaki ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cd40 Ligand ◽  
Interferon Γ ◽  
Antiapoptotic Proteins ◽  
Enhanced Production ◽  
Factor Α

Signals generated through CD28–B7 and CD40 ligand (CD40L)–CD40 interactions have been shown to be crucial for the induction of long-term allograft survivability. We have recently demonstrated that humanized anti-CD40L (hu5C8) prevents rejection of mismatched renal allografts in primates. To investigate potential mechanisms of CD40L–induced allograft acceptance, we coimmobilized hu5C8 with suboptimal amounts of anti-CD3 to stimulate CD4+ T cells. We now report that anti-CD3/CD40L costimulation results in CD28-independent activation and subsequent deletion of resting T cells. Coligation of CD3 and CD40L increased expression of CD69, CD25, and CD54 on CD4+ T cells. We also found that costimulation with anti-CD3/CD40L resulted in enhanced production of interleukin (IL)-10, interferon γ, and tumor necrosis factor α but not IL-2 or IL-6. Interestingly, after several days, anti-CD3/CD40L–mediated activation was followed by apoptosis in a significant population of cells. Consistent with that observation, anti-CD3/CD40L did not enhance the antiapoptotic proteins Bcl-2 and Bcl-xL. Further, the addition of CD28 at 24 h failed to rescue those cells induced to die after costimulation with anti-CD3/CD40L. Together, these data suggest that the graft-sparing effect of hu5C8 in vivo may result in part from early and direct effects on CD4+ T cells, including a vigorous induction of immunomodulatory cytokines and/or apoptosis of allograft-specific T cells.

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