scholarly journals CXCL9 and CXCL11 Chemokines Modulation by Peroxisome Proliferator-Activated Receptor-α Agonists Secretion in Graves’ and Normal Thyrocytes

2010 ◽  
Vol 95 (12) ◽  
pp. E413-E420 ◽  
Author(s):  
Alessandro Antonelli ◽  
Silvia Martina Ferrari ◽  
Silvia Frascerra ◽  
Cinzia Pupilli ◽  
Caterina Mancusi ◽  
...  
Keyword(s):  
Peroxisome Proliferator ◽  
Thyroid Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dependent Inhibition ◽  
Pparγ Agonists ◽  
Dose Dependent Inhibition ◽  
And Control ◽  
Dose Dependent ◽  
Stimulation Of

Context: Peroxisome proliferator-activated receptor (PPAR)-α has been shown to exert immunomodulatory effects in autoimmune disorders. However, until now, no data were present in the literature about the effect of PPARα activation on CXCL9 and CXCL11 chemokines in general or on secretion of these chemokines in thyroid cells. Objective and Design: The presence of PPARα and PPARγ has been evaluated by real-time-PCR in Graves’ disease (GD) and control cells in primary culture. Furthermore, we have tested the role of PPARα and PPARγ activation on CXCL9 and CXCL11 secretion in GD and control cells after stimulation of these chemokines secretion with IFNγ and TNFα. Results: This study shows the presence of PPARα and PPARγ in GD and control cells. A potent dose-dependent inhibition by PPARα-agonists was observed on the cytokines-stimulated secretion of CXCL9 and CXCL11 in GD and control cells. The potency of the PPARα agonists used was maximum on the secretion of CXCL9, reaching about 90% of inhibition by fenofibrate and 85% by ciprofibrate. The relative potency of the compounds was different with each chemokine; for example, gemfibrozil exerted a 55% inhibition on CXCL11, whereas it had a weaker activity on CXCL9 (40% inhibition). PPARα agonists were stronger (ANOVA, P < 0.001) inhibitors of CXCL9 and CXCL11 secretion in thyrocytes than PPARγ agonists. Conclusions: Our study shows the presence of PPARα in GD and control thyrocytes. PPARα activators are potent inhibitors of the secretion of CXCL9 and CXCL11, suggesting that PPARα may be involved in the modulation of the immune response in the thyroid.

scholarly journals CXCL9 and CXCL11 Chemokines Modulation by Peroxisome Proliferator-Activated Receptor-α Agonists Secretion in Graves’ and Normal Thyrocytes

2010 ◽  
Vol 31 (5) ◽  
pp. 780-780
Author(s):  
Alessandro Antonelli ◽  
Silvia Martina Ferrari ◽  
Silvia Frascerra ◽  
Cinzia Pupilli ◽  
Caterina Mancusi ◽  
...  
Keyword(s):  
Peroxisome Proliferator ◽  
Rt Pcr ◽  
Thyroid Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dependent Inhibition ◽  
Pparγ Agonists ◽  
Dose Dependent Inhibition ◽  
And Control ◽  
Dose Dependent

ABSTRACT Context Peroxisome proliferator-activated receptor (PPAR)-α has been shown to exert immunomodulatory effects in autoimmune disorders. However, until now, no data were present in the literature about the effect of PPARα activation on CXCL9 and CXCL11 chemokines in general or on secretion of these chemokines in thyroid cells. Objective and Design The presence of PPARα and PPARγ has been evaluated by RT-PCR in Graves’ disease (GD) and control cells in primary culture. Furthermore, we have tested the role of PPARα and PPARγ activation on CXCL9 and CXCL11 secretion in GD and control cells after stimulation of these chemokines secretion with IFNγ and TNFα. Results This study shows the presence of PPARα and PPARγ in GD and control cells. A potent dose-dependent inhibition by PPARα-agonists was observed on the cytokines-stimulated secretion of CXCL9 and CXCL11 in GD and control cells. The potency of the PPARα agonists used was maximum on the secretion of CXCL9, reaching about 90% of inhibition by fenofibrate and 85% by ciprofibrate. The relative potency of the compounds was different with each chemokine; for example, gemfibrozil exerted a 55% inhibition on CXCL11, whereas it had a weaker activity on CXCL9 (40% inhibition). PPARα agonists were stronger (ANOVA, P < 0.001) inhibitors of CXCL9 and CXCL11 secretion in thyrocytes than PPARγ agonists. Conclusions Our study shows the presence of PPARα in GD and control thyrocytes. PPARα activators are potent inhibitors of the secretion of CXCL9 and CXCL11, suggesting that PPARα may be involved in the modulation of the immune response in the thyroid.

scholarly journals The role of GTP in prostaglandin E1 stimulation of adenylate cyclase in platelet membranes

1983 ◽  
Vol 214 (1) ◽  
pp. 231-234 ◽  
Author(s):  
J M Stein ◽  
B R Martin
Keyword(s):  
Adenylate Cyclase ◽  
Prostaglandin E1 ◽  
Platelet Membrane ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Stimulation Of

Adenylate cyclase activity in platelet membrane preparations was measured in the presence of prostaglandin E1 (PGE1), GTP and a non-hydrolysable analogue of GDP, guanosine 5′-[beta-thio]diphosphate (GDP[beta S]). A dose-dependent inhibition of adenylate cyclase by GDP[beta S] was observed that could be reversed either by adding increased amounts of GTP or of PGE1.

Investigation on the antibacterial activity of electronic cigarette liquids (ECLs): a proof of concept study

2020 ◽  
Vol 21 ◽  
Author(s):  
Virginia Fuochi ◽  
Massimo Caruso ◽  
Rosalia Emma ◽  
Aldo Stivala ◽  
Riccardo Polosa ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Species ◽  
A549 Cells ◽  
Bactericidal Effect ◽  
Minimal Bactericidal Concentration ◽  
Viability Assay ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Background: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. Objective: The effect of the combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. Methods: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. Results: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. A higher activity was correlated to the presence of flavors and nicotine. Discussion: In most cases the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. Conclusion: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.

scholarly journals Proteoglycan and glycosaminoglycan synthesis in embryonic mouse salivary glands: effects of beta-D-xyloside, an inhibitor of branching morphogenesis.

1983 ◽  
Vol 96 (5) ◽  
pp. 1443-1450 ◽  
Author(s):  
H A Thompson ◽  
B S Spooner
Keyword(s):  
Salivary Glands ◽  
Dermatan Sulfate ◽  
Branching Morphogenesis ◽  
Proteoglycan Synthesis ◽  
Embryonic Mouse ◽  
Glycosaminoglycan Synthesis ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Stimulation Of

The proteoglycans and glycosaminoglycans synthesized by embryonic mouse salivary glands during normal morphogenesis and in the presence of beta-xyloside, an inhibitor of branching morphogenesis, have been partially characterized. Control and rho-nitrophenyl-beta-D-xyloside-treated salivary rudiments synthesize proteoglycans that are qualitatively similar, based on mobility on Sepharose CL-4B under dissociative conditions and glycosaminoglycan composition. However, beta-xyloside inhibits total proteoglycan-associated glycosaminoglycan synthesis by 50%, and also stimulates synthesis of large amounts of free chondroitin (dermatan) sulfate. This free glycosaminoglycan accounts for the threefold stimulation of total glycosaminoglycan synthesis in beta-xyloside-treated cultures. Several observations suggest that the disruption of proteoglycan synthesis rather than the presence of large amounts of free glycosaminoglycan is responsible for the inhibition of branching morphogenesis. (a) We have been unable to inhibit branching activity by adding large amounts of chondroitin (dermatan) sulfate, extracted from beta-xyloside-treated cultures, to the medium of salivary rudiments undergoing morphogenesis. (b) In the range of 0.1-0.4 mM beta-xyloside, the dose-dependent inhibition of branching morphogenesis is directly correlated with the inhibition of proteoglycan synthesis. The stimulation of free glycosaminoglycan synthesis is independent of dose in this range, since stimulation is maximal even at the lowest concentration used, 0.1 mM. The data strongly suggest that the inhibition of branching morphogenesis is caused by the disruption of proteoglycan synthesis in beta-xyloside-treated salivary glands.

scholarly journals β (CCL2) and α (CXCL10) chemokine modulations by cytokines and peroxisome proliferator-activated receptor-α agonists in Graves' ophthalmopathy

2012 ◽  
Vol 213 (2) ◽  
pp. 183-191 ◽  
Author(s):  
Alessandro Antonelli ◽  
Silvia Martina Ferrari ◽  
Silvia Frascerra ◽  
Ilaria Ruffilli ◽  
Cinzia Pupilli ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Graves Ophthalmopathy ◽  
Primary Fibroblasts ◽  
Pparγ Agonists ◽  
Factor Α ◽  
Orbital Fibroblasts ◽  
Ifnγ And Tnfα

No data are present in the literature about the effect of cytokines on the prototype β chemokine (C-C motif) ligand 2 (CCL2) or of peroxisome proliferator-activated receptor α (PPARα (PPARA)) activation on CCL2 and CXCL10 chemokines secretion in fibroblasts or preadipocytes in Graves' ophthalmopathy (GO). We have tested the effect of interferon γ (IFNγ (IFNG)) and tumor necrosis factor α (TNFα) on CCL2, and for comparison on the prototype α chemokine (C-X-C motif) ligand 10 (CXCL10), and the possible modulatory role of PPARα activation on secretion of these chemokines in normal and GO fibroblasts or preadipocytes in primary cell cultures. This study shows that IFNγ alone, or in combination with TNFα, stimulates the secretion of CCL2 in primary orbital fibroblasts or preadipocytes from patients with GO at levels similar to those observed in controls. IFNγ and TNFα also stimulated CXCL10 chemokine secretion as expected. The presence of PPARα and PPARγ (PPARG) in primary fibroblasts or preadipocytes of patients with GO has been confirmed. PPARα activators were able to inhibit the secretion of CXCL10 and CCL2, while PPARγ activators were confirmed to be able to inhibit CXCL10 but had no effect on CCL2. PPARα activators were stronger inhibitors of chemokine secretions than PPARγ agonists. In conclusion, CCL2 and CXCL10 are modulated by IFNγ and TNFα in GO. PPARα activators inhibit the secretion of the main prototype α (CXCL10) and β (CCL2) chemokines in GO fibroblasts or preadipocytes, suggesting that PPARα may be involved in the modulation of the immune response in GO.

scholarly journals PPARγ1 attenuates cytosol to membrane translocation of PKCα to desensitize monocytes/macrophages

2007 ◽  
Vol 176 (5) ◽  
pp. 681-694 ◽  
Author(s):  
Andreas von Knethen ◽  
Mathias Soller ◽  
Nico Tzieply ◽  
Andreas Weigert ◽  
Axel M. Johann ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Underlying Mechanism ◽  
Nuclear Factor Κb ◽  
Peroxisome Proliferator ◽  
Membrane Translocation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Protein Interaction ◽  
Tnf Α ◽  
Dependent Inhibition ◽  
Pparγ Agonists

Recently, we provided evidence that PKCα depletion in monocytes/macrophages contributes to cellular desensitization during sepsis. We demonstrate that peroxisome proliferator–activated receptor γ (PPARγ) agonists dose dependently block PKCα depletion in response to the diacylglycerol homologue PMA in RAW 264.7 and human monocyte–derived macrophages. In these cells, we observed PPARγ-dependent inhibition of nuclear factor-κB (NF-κB) activation and TNF-α expression in response to PMA. Elucidating the underlying mechanism, we found PPARγ1 expression not only in the nucleus but also in the cytoplasm. Activation of PPARγ1 wild type, but not an agonist-binding mutant of PPARγ1, attenuated PMA-mediated PKCα cytosol to membrane translocation. Coimmunoprecipitation assays pointed to a protein–protein interaction of PKCα and PPARγ1, which was further substantiated using a mammalian two-hybrid system. Applying PPARγ1 mutation and deletion constructs, we identified the hinge helix 1 domain of PPARγ1 that is responsible for PKCα binding. Therefore, we conclude that PPARγ1-dependent inhibition of PKCα translocation implies a new model of macrophage desensitization.

Prejunctional inhibition of vasoactive intestinal peptide release

1987 ◽  
Vol 253 (1) ◽  
pp. G7-G12 ◽  
Author(s):  
J. R. Grider ◽  
G. M. Makhlouf
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Muscle Relaxation ◽  
Dependent Manner ◽  
Basal Tone ◽  
Peptide Release ◽  
Dependent Inhibition ◽  
Motor Nerves ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

The role of vasoactive intestinal peptide (VIP) and its homologue, peptide histidine isoleucine (PHI), as neurotransmitters of inhibitory motor nerves of the gut, were examined in strips of guinea pig taenia coli and gastric fundic muscle. The stoichiometry of VIP release and muscle relaxation was determined in the presence and absence of the bee venom peptide, apamin, and the existence of prejunctional VIP/PHI receptors capable of regulating VIP/PHI release was explored. In both types of muscle, relaxation induced by field stimulation was proportional to the amount of VIP released. Apamin inhibited relaxation and VIP release in a dose-dependent manner: maximal relaxation was inhibited by 85–96% at 10(-7)-10(-6) M apamin. Analysis of residual responses showed that apamin did not affect the stoichiometry of VIP release and muscle relaxation. Because apamin had no effect on basal tone or on relaxation induced by exogenous VIP, its effect on neurally induced relaxation was attributed to inhibition of VIP release. Both secretin and PHI inhibited neurally induced VIP release in the two types of muscle. At the optimal concentration of 10(-7) M, secretin inhibited VIP release by 52%, whereas the closer neural homologue, PHI, abolished VIP release. The dose-dependent inhibition of VIP release by PHI, which is cosynthesized and coreleased with VIP, indicates the existence of prejunctional inhibitory VIP/PHI autoreceptors capable of regulating VIP/PHI release.

Russell's viper venom stimulates insulin secretion from rat islets of Langerhans

1993 ◽  
Vol 136 (1) ◽  
pp. 27-33 ◽  
Author(s):  
P. M. Jones ◽  
F. M. Mann
Keyword(s):  
Insulin Secretion ◽  
Islets Of Langerhans ◽  
Prolonged Exposure ◽  
Blue Dye ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Russell’S Viper ◽  
Rat Islets Of Langerhans ◽  
Dose Dependent ◽  
Stimulation Of

ABSTRACT Burmese Russell's viper venom (RVV) caused a dose-and temperature-dependent stimulation of insulin secretion from islets of Langerhans isolated from rat pancreas by collagenase digestion. RVV stimulated both basal and glucose-induced insulin secretion at concentrations which did not compromise islet cell viability as assessed by exclusion of trypan blue dye. The effects of RVV on insulin secretion could not be attributed to the activation of protein kinase C (PKC), since down-regulation of PKC by prolonged exposure to a tumour-promoting phorbol ester did not abolish subsequent secretory responses to RVV. However, RVV-induced insulin secretion was inhibited in the absence of extracellular Ca2 +, and RVV did not stimulate insulin secretion from Ca2+-clamped electrically permeabilized islets at either substimulatory (50 nmol/l) or stimulatory (10 μmol/l) concentrations of Ca2 +, suggesting that changes in cytosolic Ca2+ are important in the stimulation of insulin secretion by RVV. The phospholipase A2 (PLA2) inhibitor quinacrine caused a dose-dependent inhibition of RVV-induced insulin secretion, suggesting that the activation of PLA2, perhaps in response to Ca2+ influx, may be partially responsible for RVV-induced insulin secretion. Journal of Endocrinology (1993) 136, 27–33

Anti-nociceptive activity of a few structurally related trimethoxy flavones and possible mechanisms involved

2016 ◽  
Vol 27 (2) ◽  
Author(s):  
Jagan Nadipelly ◽  
Vijaykumar Sayeli ◽  
Parimala Kadhirvelu ◽  
Jaikumar Shanmugasundaram ◽  
Binoy Varghese Cheriyan ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Hot Water ◽  
Dependent Manner ◽  
Tail Immersion ◽  
Dopaminergic Mechanisms ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Definite Role

AbstractThe present study was designed to investigate the anti-nociceptive activity of a few structurally related trimethoxy flavones (7,2′,3′-TMF, 7,2′,4′-TMF, 7,3′,4′-TMF and 7,5,4′-TMF) and the possible mechanisms involved.Anti-nociceptive activity was evaluated in mice by employing acetic acid-induced writhing, formalin-induced nociception and hot water tail immersion methods. The involvement of opioid, GABAergic, tryptaminergic, adrenergic and dopaminergic mechanisms and KTrimethoxy flavones exhibited a significant and dose-dependent inhibition of acetic acid writhing. The paw-licking response time was reduced both in the early and late phases of formalin nociception in a dose-dependent manner by trimethoxy flavones. A significant increase in tail withdrawal latency time was also observed after trimethoxy flavones treatment. These observations revealed the potential anti-nociceptive action of the investigated trimethoxy flavones. Pretreatment with naloxone and bicuculline significantly attenuated the reduction of abdominal constrictions produced by all the tested trimethoxy flavones indicating a definite role of opioid and GABAergic mechanisms in the anti-nociceptive effect of trimethoxy flavones. The anti-nociceptive action elicited by various trimethoxy flavones was differently modulated by glibenclamide, ondansetron, yohimbine and sulpiride.The investigated trimethoxy flavones exhibited promising anti-nociceptive activity in various nociceptive models, and multiple mechanisms are involved in the anti-nociceptive activity of these compounds.

Regulation of phosphatidylcholine and phosphatidylethanolamine synthesis in rat hepatocytes by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)

2002 ◽  
Vol 362 (1) ◽  
pp. 97-104 ◽  
Author(s):  
Martin HOUWELING ◽  
Wil KLEIN ◽  
Math J. H. GEELEN
Keyword(s):  
Cellular Uptake ◽  
Rat Hepatocytes ◽  
Cellular Level ◽  
Membrane Phospholipids ◽  
Main Target ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

The present study was undertaken to study the role of AMP-activated kinase (AMPK) in the biosynthesis of two major membrane phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Incubation of rat hepatocytes with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an activator of AMPK, produced dose-dependent inhibition of the incorporation of [3H]choline and [3H]ethanolamine into PC and PE, respectively. Determination of the cellular uptake of choline and ethanolamine showed that the reduced synthesis of PC and PE did not result from impaired uptake of these two precursors. The decreased synthesis of PC was not mirrored by a reduction in the activities of the enzymes of the CDP-choline pathway. The diminution of PE biosynthesis, however, was paralleled by a depressed activity of CTP:phosphoethanolamine cytidylyltransferase (ET), the pace-setting enzyme of the CDP-ethanolamine pathway. AICAR treatment of hepatocytes stimulated the conversion of choline into betaine, indicating that reduced PC synthesis most probably resulted from a decrease in the availability of choline. In addition, AICAR induced a 50% reduction in the cellular level of diacylglycerols, which may further impair the synthesis of PC and PE. The results thus indicate that AICAR inhibits the biosynthesis of PC and PE and that the effect is exerted at different sites in the two pathways. Increased oxidation of choline to betaine is the main target of AICAR in the PC pathway, whereas inhibition of ET activity is the locus of AICAR action in the PE pathway.

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