Altered anti-inflammatory response of mononuclear cells to neuropeptide PACAP is associated with deregulation of NF-κB in chronic pancreatitis

2008 ◽  
Vol 294 (1) ◽  
pp. G50-G57 ◽  
Author(s):  
Christoph W. Michalski ◽  
Federico Selvaggi ◽  
Michael Bartel ◽  
Tomas Mitkus ◽  
Andrej Gorbachevski ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Laser Capture Microdissection ◽  
Mononuclear Cells ◽  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Peripheral Blood Mononuclear ◽  
Pancreatic Acini ◽  
Neuroimmune Interactions ◽  
Anti Inflammatory ◽  
Laser Capture

Although it is recognized that neurogenic influences contribute to progression of chronic inflammatory diseases, the molecular basis of neuroimmune interactions in the pathogenesis of chronic pancreatitis (CP) is not well defined. Here we report that responsiveness of peripheral blood mononuclear cells (PBMC) to the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is altered in CP. Expression of PACAP and its receptors in human CP was analyzed with quantitative RT-PCR, laser-capture microdissection, and immunohistochemistry. Regulation of PACAP expression was studied in coculture systems using macrophages and acinar cells. Responsiveness of donor and CP PBMC to PACAP was determined based on cytokine profiles and NF-κB activation of LPS- or LPS+PACAP-exposed cells. Although donor and CP PBMC responded equally to LPS, PACAP-mediated counteraction of LPS-induced cytokine response was switched from inhibiting TNF-α to decreasing IL-1β and increasing IL-10 secretion. The change of PACAP-mediated anti-inflammatory pattern was associated with altered activation of NF-κB: compared with LPS alone, a combination of LPS and PACAP had no effect on NF-κB p65 nuclear translocation in CP PBMC, whereas NF-κB was significantly decreased in donor PBMC. According to laser-capture microdissection and coculture experiments, PBMC also contributed to generation of a PACAP-rich intrapancreatic environment by upregulating PACAP expression in macrophages encountering apoptotic pancreatic acini. The nociceptive status of CP patients correlated with pancreatic PACAP levels and with IL-10 bias of PACAP-exposed CP PBMC. Thus the ability of PBMC to produce and to respond to PACAP might influence neuroimmune interactions that regulate pain and inflammation in CP.

Combinatorial Action of Triterpenoid, Flavonoid, and Alkaloid on Inflammation

2019 ◽  
Vol 14 (8) ◽  
pp. 1934578X1986887
Author(s):  
Vidya Sabu ◽  
Jasmine Peter ◽  
Aswathy Indira Bai Sasidharan Nair ◽  
Santhi Krishnan ◽  
Lal Preethi Sathyaseelan Suja ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Mononuclear Cells ◽  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Human Peripheral Blood ◽  
Synergistic Effects ◽  
Signaling Cascade ◽  
Peripheral Blood Mononuclear ◽  
Cox 2 ◽  
Anti Inflammatory

In the present study, the synergistic effects of BASk, a combination of betulinic acid (B), apigenin (A), and skimmianine (Sk) in the ratio of 1:1:1, were studied to construct a novel drug mixture against inflammation via the TLR4-nuclear factor Kappa light chain enhancer of activated B cells (NFκB) signaling pathway. In silico drug likeness and docking studies recommended 3 bioactive compounds as suitable ligands for drug development. BASk inhibited TLR4 from its dimerization with MD2 and blocked the TLR4 signaling cascade. Reduced nuclear translocation of NFκB inhibited the release of pro-inflammatory mediators (IL-1β and TNF-α), COX-2 expression, and PGE2. Similarly, BASk exerted its protective role by reducing pro-inflammatory mediators and elevating anti-inflammatory cytokine, IL-10. This confirms the inhibiting potential of BASk in the activation of the TLR4-NFκB signaling cascade. Thus, BASk was superior in its anti-inflammatory effect on oxidized low density lipoprotein (ox-LDL) induced human peripheral blood mononuclear cells than its individual components synergistically. Since BASk inhibited COX-2 expression and further release of PGE2, it is a potent therapeutic agent with better efficacy against inflammation because COX-2 is the target site for treating inflammatory diseases. Thus, it can be clearly stated that this innovation will be a breakthrough in the treatment of inflammatory diseases.

Dipyridamole decreases inflammatory metalloproteinase-9 expression and release by human monocytes

2013 ◽  
Vol 109 (02) ◽  
pp. 280-289 ◽  
Author(s):  
Maria Annunziata Carluccio ◽  
Mariangela Pellegrino ◽  
Nadia Calabriso ◽  
Carlo Storelli ◽  
Giuseppe Martines ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Mononuclear Cells ◽  
Nuclear Translocation ◽  
Human Peripheral Blood ◽  
Antiplatelet Agent ◽  
Guanosine Monophosphate ◽  
Human Monocytes ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Anti Inflammatory

SummaryMatrix metalloproteinase (MMP)-9 plays an important role in stroke by accelerating matrix degradation, disrupting the blood-brain barrier and increasing infarct size. Dipyridamole is an antiplatelet agent with recognised benefits in ischaemic stroke prevention. In addition to its antiplatelet properties, recent studies have reported that dipyridamole also features anti-inflammatory and anti-oxidant properties. We therefore investigated whether dipyridamole can ameliorate the proinflammatory profile of human monocytes, a source of MMP-9 in stroke, in terms of regulation of MMP-9 activity and expression, and explored underlying mechanisms. Human peripheral blood mononuclear cells (PBMC) and U937 cells were treated with increasing concentrations of dipyridamole (up to 10 µg/ml) for 60 minutes before stimulation with tumour necrosis factor (TNF)-α or phorbol myristate acetate (PMA). Exposure of PBMC and U937 to dipyridamole reduced TNF-α- and PMA-induced MMP-9 activity and protein release as well as MMP-9 mRNA, without significantly affecting the release of TIMP-1. This inhibitory effect was independent of dipyridamole-induced cyclic adeno-sine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) increase. Correspondingly, dipyridamole also significantly inhibited TNF-α-induced nuclear factor (NF)-κB activation and nuclear translocation of the p65 NF-κB subunit through a mechanism involving the inhibition of IkBα degradation and p38 MAPK activation. In conclusion, dipyridamole, at therapeutically achievable concentrations, reduces the expression and release of MMP-9 through a mechanism involving p38 MAPK and NF-κB inhibition. These results indicate that dipyridamole exerts anti-inflammatory properties in human monocytes that may favourably contribute to its actions in the secondary prevention of stroke, independent of its antiplatelet properties.

scholarly journals Anti-Inflammatory Activity of a CB2 Selective Cannabinoid Receptor Agonist: Signaling and Cytokines Release in Blood Mononuclear Cells

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 64
Author(s):  
Antonella Capozzi ◽  
Daniela Caissutti ◽  
Vincenzo Mattei ◽  
Francesca Gado ◽  
Stefano Martellucci ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Cannabinoid Receptor ◽  
Inflammatory Diseases ◽  
Jurkat Cells ◽  
Parp Cleavage ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Anti Inflammatory ◽  
Apoptotic Activity

The endocannabinoid system (ECS) exerts immunosuppressive effects, which are mostly mediated by cannabinoid receptor 2 (CBR2), whose expression on leukocytes is higher than CBR1, mainly localized in the brain. Targeted CBR2 activation could limit inflammation, avoiding CBR1-related psychoactive effects. Herein, we evaluated in vitro the biological activity of a novel, selective and high-affinity CBR2 agonist, called JT11, studying its potential CBR2-mediated anti-inflammatory effect. Trypan Blue and MTT assays were used to test the cytotoxic and anti-proliferative effect of JT11 in Jurkat cells. Its pro-apoptotic activity was investigated analyzing both cell cycle and poly PARP cleavage. Finally, we evaluated its impact on LPS-induced ERK1/2 and NF-kB-p65 activation, TNF-α, IL-1β, IL-6 and IL-8 release in peripheral blood mononuclear cells (PBMCs) from healthy donors. Selective CB2R antagonist SR144528 and CBR2 knockdown were used to further verify the selectivity of JT11. We confirmed selective CBR2 activation by JT11. JT11 regulated cell viability and proliferation through a CBR2-dependent mechanism in Jurkat cells, exhibiting a mild pro-apoptotic activity. Finally, it reduced LPS-induced ERK1/2 and NF-kB-p65 phosphorylation and pro-inflammatory cytokines release in human PBMCs, proving to possess in vitro anti-inflammatory properties. JT11 as CBR2 ligands could enhance ECS immunoregulatory activity and our results support the view that therapeutic strategies targeting CBR2 signaling could be promising for the treatment of chronic inflammatory diseases.

Meta-inflammation in monocytes of patients with Acute Coronary Syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Canonico ◽  
R Vinci ◽  
D Pedicino ◽  
E Pisano ◽  
P Ciampi ◽  
...  
Keyword(s):  
Protein Identification ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Glycolytic Enzyme ◽  
Potential Interaction ◽  
Limiting Factor ◽  
Funding Source ◽  
Peripheral Blood Mononuclear ◽  
Coronary Syndrome ◽  
Key Enzyme

Abstract Background Several studies suggest that an alteration of monocyte metabolism might be implicated in inflammatory diseases. Enhanced glycolysis might be a hallmark of pro-inflammatory monocyte subsets. Improved glycolysis enables the immune cells to generate sufficient ATP and biosynthetic intermediates to carry out its particular effector functions. For macrophages this includes phagocytosis and inflammatory cytokine production. Pyruvate Kinase isozyme M2 (PKM-2) catalyzes the final step of glycolysis producing pyruvate and ATP. Latest studies have shown that a member of Jumonji family (JMJD8) acts as a positive regulator in TNF-induced NF-kB signaling leading to pro-inflammatory pathways in macrophages and is involved in angiogenesis and cellular metabolism through interacting with PKM-2 in endothelial cells. Purpose The aims of the study are to assess the expression of the glycolytic key enzyme PKM-2 in CD14+ monocytes obtained from patients with non-ST-elevation myocardial infarction (NSTEMI) or with stable angina (SA). Furthermore, the expression of JMJD8 was evaluated. Methods 30 patients with NSTEMI and 30 patients with SA were enrolled. Peripheral blood mononuclear cells were obtained from whole blood samples. For cytoplasmatic protein identification, cells were fixed and permeabilized and then incubated with fluorochrome-conjugated mAbs anti-CD14, anti-PKM-2 and anti-JMJD8. For analysis we used Two-tailed Mann-Whitney non parametric Comparison test. Results CD14+ monocytes from NSTEMI patients showed reduced expression of the key glycolytic enzyme PKM-2 as compared to CD14+ monocytes from SA patients (p=0.02) (Figure 1). JMJD8 expression in NSTEMI patients is increased compared with SA patients (p=0.02) (Figure 2). Conclusion This study introduces a role for immune-metabolism in the immunity dysregulation described in ACS patients and provides novel insights into the mechanisms responsible for coronary instability. Taking their potential interaction into account, our data suggest that in acute setting glycolysis key enzyme PKM2 expression is downregulated. Besides, JMJD8 protein levels increase in NSTEMI patients acting as potential limiting factor of PKM2 function. Moreover, our data propose the potential roles of immune-metabolism to detect novel therapeutic targets, associated with an accurate patient stratification based on immune-metabolic profiles, for prevention and treatment of atherosclerosis, in the perspective of a personalized medicine approach. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Fondazione Policlinico A. Gemelli

scholarly journals Anti-inflammatory genes in PBMCs post-spontaneous intracerebral hemorrhage

2021 ◽  
Vol 12 (1) ◽  
pp. 58-66
Author(s):  
Doan Nguyen ◽  
Vi Tran ◽  
Alireza Shirazian ◽  
Cruz Velasco-Gonzalez ◽  
Ifeanyi Iwuchukwu
Keyword(s):  
Intracerebral Hemorrhage ◽  
Negative Correlation ◽  
Mononuclear Cells ◽  
Inflammatory Cells ◽  
Favorable Outcome ◽  
Hospital Length Of Stay ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Hematoma Volume ◽  
Peripheral Blood Mononuclear ◽  
Anti Inflammatory

Abstract Background Neuroinflammation is important in the pathophysiology of spontaneous intracerebral hemorrhage (ICH) and peripheral inflammatory cells play a role in the clinical evolution and outcome. Methodology Blood samples from ICH patients (n = 20) were collected at admission for 5 consecutive days for peripheral blood mononuclear cells (PBMCs). Frozen PBMCs were used for real-time PCR using Taqman probes (NFKB1, SOD1, PPARG, IL10, NFE2L2, and REL) and normalized to GAPDH. Data on hospital length of stay and modified Rankin score (MRS) were collected with 90-day MRS ≤ 3 as favorable outcome. Statistical analysis of clinical characteristics to temporal gene expression from early to delayed timepoints was compared for MRS groups (favorable vs unfavorable) and hematoma volume. Principle findings and results IL10, SOD1, and REL expression were significantly higher at delayed timepoints in PBMCs of ICH patients with favorable outcome. PPARG and REL increased between timepoints in patients with favorable outcome. NFKB1 expression was not sustained, but significantly decreased from higher levels at early onset in patients with unfavorable outcome. IL10 expression showed a negative correlation in patients with high hematoma volume (>30 mL). Conclusions and significance Anti-inflammatory, pro-survival regulators were highly expressed at delayed time points in ICH patients with a favorable outcome, and IL10 expression showed a negative correlation to high hematoma volume.

scholarly journals In Vitro Anti-Inflammatory and Immunomodulatory Activities of an Extract from the Roots of Bupleurum rotundifolium

Medicines ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 101 ◽  
Author(s):  
Cholet ◽  
Decombat ◽  
Vareille-Delarbre ◽  
Gainche ◽  
Berry ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Polymorphonuclear Neutrophils ◽  
Ros Production ◽  
Peripheral Blood Mononuclear ◽  
Aerial Parts ◽  
Bupleurum Scorzonerifolium Willd ◽  
Anti Inflammatory ◽  
Inflammatory Profile ◽  
Bupleurum Scorzonerifolium

Background: Some Bupleurum species, such as the Bupleurum chinense DC. or the Bupleurum scorzonerifolium Willd have been extensively studied (especially their roots) for the treatment of inflammation. In contrast, only compounds extracted from the aerial parts of Bupleurum rotundifolium have been studied and showed anti-inflammatory or antiproliferative activities. This study was conducted to investigate the antioxidant, anti-inflammatory, and immunomodulatory effects of Bupleurum rotundifolium roots. Methods: To tackle the various aspects of inflammation, we studied in vitro a methanolic extract from the roots of Bupleurum rotundifolium on peripheral blood mononuclear cells (PBMCs), polymorphonuclear neutrophils (PMNs), and the monocytic cells THP-1. Its antioxidant capacities and iron-chelating activity were assessed. The extract was tested on THP-1 differentiation, reactive oxygen species (ROS) production by leukocytes, neutrophils chemotaxis, cytokines, PGE2 production, and NF-κB activation in PBMCs. Results: The extract showed a decreased ROS production in stimulated cells. It increased PBMC chemokine secretion and up-regulated the differentiation of THP-1 monocytes into macrophage-like cells, indicating a potential interest of the extract in the resolution of acute inflammation. In addition, the analysis of cytokine production suggests that Bupleurum rotundifolium has immunomodulatory properties. Conclusions: Cytokines secretion, especially IL-1β and IL-12p70, provided us with a set of indicators suggesting that the extract might be able to drive the polarization of macrophages and lymphocytes toward a Th2 anti-inflammatory profile in excessive inflammation.

scholarly journals The immunoregulatory function of peripheral blood CD71+ erythroid cells in systemic-onset juvenile idiopathic arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hikaru Kanemasa ◽  
Masataka Ishimura ◽  
Katsuhide Eguchi ◽  
Tamami Tanaka ◽  
Etsuro Nanishi ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Active Phase ◽  
Serum Levels ◽  
Cell Interaction ◽  
Erythroid Cells ◽  
Peripheral Blood Mononuclear ◽  
Systemic Onset

AbstractCD71+ erythroid cells (CECs) are recognized to have an immunoregulatory function via direct cell–cell interaction and soluble mediators. Circulating CECs appear in newborns or patients with hemolytic and cardiopulmonary disorders. To assess the biological role of CECs in systemic inflammation, we studied the gene expression and function in systemic-onset juvenile idiopathic arthritis (SoJIA). Peripheral blood mononuclear cells of SoJIA patients expressed upregulated erythropoiesis-related genes. It represented the largest expansion of CECs during active phase SoJIA among other inflammatory diseases. Despite the opposing roles of erythropoietin and hepcidin in erythropoiesis, both serum levels were in concert with the amounts of SoJIA-driven CECs. Circulating CECs counts in inflammatory diseases were positively correlated with the levels of C-reactive protein, IL-6, IL-18, or soluble TNF receptors. Co-culture with active SoJIA-driven CECs suppressed secretions of IL-1β, IL-6, and IL-8 from healthy donor monocytes. The top upregulated gene in SoJIA-driven CECs was ARG2 compared with CECs from cord blood controls, although cytokine production from monocytes was suppressed by co-culture, even with an arginase inhibitor. CECs are driven to the periphery during the acute phase of SoJIA at higher levels than other inflammatory diseases. Circulating CECs may control excessive inflammation via the immunoregulatory pathways, partly involving arginase-2.

scholarly journals Liposome/gold hybrid nanoparticle encoded with CoQ10 (LGNP-CoQ10) suppressed rheumatoid arthritis via STAT3/Th17 targeting

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241080
Author(s):  
Jooyeon Jhun ◽  
Jeonghyeon Moon ◽  
Jaeyoon Ryu ◽  
Yonghee Shin ◽  
Seangyoun Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Human Peripheral Blood ◽  
Treated Group ◽  
Hybrid Nanoparticles ◽  
Peripheral Blood Mononuclear ◽  
Hematoxylin And Eosin ◽  
Anti Inflammatory ◽  
Safranin O

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a fat-soluble antioxidant. Although CoQ10 has not been approved as medication by the Food and Drug Administration, it is widely used in dietary supplements. Some studies have shown that CoQ10 has anti-inflammatory effects on various autoimmune disorders. In this study, we investigated the anti-inflammatory effects of liposome/gold hybrid nanoparticles encoded with CoQ10 (LGNP-CoQ10). Both CoQ10 and LGNP-CoQ10 were administered orally to mice with collagen-induced arthritis (CIA) for 10 weeks. The inflammation pathology of joint tissues of CIA mice was then analyzed using hematoxylin and eosin and Safranin O staining, as well as immunohistochemistry analysis. We obtained immunofluorescence staining images of spleen tissues using confocal microscopy. We found that pro-inflammatory cytokines were significantly decreased in LGNP-CoQ10 injected mice. Th17 cell and phosphorylated STAT3-expressed cell populations were also decreased in LGNP-CoQ10 injected mice. When human peripheral blood mononuclear cells (PBMCs) were treated with CoQ10 and LGNP-CoQ10, the IL-17 expression of PBMCs in the LGNP-CoQ10-treated group was significantly reduced. Together, these results suggest that LGNP-CoQ10 has therapeutic potential for the treatment of rheumatoid arthritis.

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