scholarly journals A Trypsin-Sensitive Proteoglycan from the Tapeworm Hymenolepis diminuta Inhibits Murine Neutrophil Chemotaxis in vitro by Suppressing p38 MAP Kinase Activation

2018 ◽  
Vol 11 (2) ◽  
pp. 136-149 ◽  
Author(s):  
Nicholas Graves ◽  
Vivek P. Venu ◽  
Bryan G. Yipp ◽  
Björn Petri ◽  
Simon Hirota ◽  
...  
Keyword(s):  
Interleukin 10 ◽  
Leukotriene B4 ◽  
P38 Map Kinase ◽  
Hymenolepis Diminuta ◽  
Mitogen Activated Protein Kinase ◽  
Helminth Parasites ◽  
Neutrophil Chemotaxis ◽  
Sodium Metaperiodate ◽  
Inflammatory Conditions

It has emerged that neutrophils can play important roles in the host response following infection with helminth parasites. Mice infected with the tapeworm, Hymenolepis diminuta, are protected from some inflammatory conditions, accompanied by reduced neutrophil tissue infiltration. Thus, the ability of a phosphate-buffered saline-soluble extract of the worm (H. diminuta extract [HdE]) was tested for (1) its ability to activate murine neutrophils (Ca2+ mobilization, reactive oxygen species (ROS) and cytokine production); and (2) affect neutrophil chemotaxis in vitro to the penta-peptide, WKYMVm, the chemokine, KC, and leukotriene B4. HdE was not cytotoxic to neutrophils, elicited a Ca2+ response and ROS, but not, cytokine (KC, interleukin-10, tumour necrosis factor-α) generation. HdE is not a chemotactic stimulus for murine neutrophils. However, a heat- and trypsin-sensitive, acid-insensitive proteoglycan (sensitive to sodium metaperiodate) in the HdE significantly reduced neutrophil chemotaxis towards WKYMVm or KC, but not LTB4. The latter suggested that the HdE interfered with p38 mitogen-activated protein kinase signalling, which is important in WKYMVm chemotaxis. Corroborating this, immunoblotting revealed reduced phosphorylated p38, and the downstream signal heat-shock protein-27, in protein extracts from HdE + WkYMVm treated cells compared to those exposed to the penta-peptide only. We speculate that HdE can be used to modify the outcome of neutrophilic disease and that purification of the bioactive proteoglycan(s) from the extract could be used as a template to design immunomodulatory drugs targeting neutrophils.

scholarly journals Human Monocyte Subsets at Homeostasis and Their Perturbation in Numbers and Function in Filarial Infection

2014 ◽  
Vol 82 (11) ◽  
pp. 4438-4446 ◽  
Author(s):  
Roshanak Tolouei Semnani ◽  
Vanessa Moore ◽  
Sasisekhar Bennuru ◽  
Renee McDonald-Fleming ◽  
Sundar Ganesan ◽  
...  
Keyword(s):  
Wuchereria Bancrofti ◽  
Human Monocyte ◽  
Interleukin 10 ◽  
Alternative Activation ◽  
Helminth Parasites ◽  
Monocyte Subsets ◽  
Filarial Infection ◽  
Content Type ◽  
And Function

ABSTRACTTo characterize the function and plasticity of the major human circulating monocyte populations and to explore their role in systemic helminth infection, highly purified (by flow-based sorting) human monocyte subsets (CD14hi/CD16neg[classical], CD14+ or hi/CD16med[intermediate], and CD14neg/CD16hi[nonclassical]) were examined at homeostasis and after activation. Among these three subsets the classical and intermediate subsets were found to be the major sources of inflammatory and regulatory cytokines, as well as cytokines/chemokines associated with alternative activation, whereas the nonclassical and classical populations demonstrated an ability to transmigrate through endothelial monolayers. Moreover, it was primarily the classical subset that was the most efficient in promoting autologous T cell proliferation. The distribution of these subsets changed in the context of a systemic helminth (Wuchereria bancrofti) infection such that patent infection altered the frequency and distribution of these monocyte subsets with the nonclassical monocytes being expanded (almost 2-fold) in filarial infection. To understand further the filarial/monocyte interface,in vitromodeling demonstrated that the classical subset internalized filarial antigens more efficiently than the other two subsets but that the parasite-driven regulatory cytokine interleukin-10 was exclusively coming from the intermediate subset. Our data suggest that monocyte subsets have a differential function at homeostasis and in response to helminth parasites.

scholarly journals Haemophilus ducreyi-Induced Interleukin-10 Promotes a Mixed M1 and M2 Activation Program in Human Macrophages

2012 ◽  
Vol 80 (12) ◽  
pp. 4426-4434 ◽  
Author(s):  
Wei Li ◽  
Barry P. Katz ◽  
Stanley M. Spinola
Keyword(s):  
Macrophage Polarization ◽  
Interleukin 10 ◽  
Human Infection ◽  
Haemophilus Ducreyi ◽  
Mitogen Activated Protein Kinase ◽  
Surface Markers ◽  
Microbial Infection ◽  
Bacterial Killing ◽  
Content Type

ABSTRACTDuring microbial infection, macrophages are polarized to classically activated (M1) or alternatively activated (M2) cells in response to microbial components and host immune mediators. Proper polarization of macrophages is critical for bacterial clearance. To study the role of macrophage polarization duringHaemophilus ducreyiinfection, we analyzed a panel of macrophage surface markers in skin biopsy specimens of pustules obtained from experimentally infected volunteers. Lesional macrophages expressed markers characteristic of both M1 and M2 polarization. Monocyte-derived macrophages (MDM) also expressed a mixed M1 and M2 profile of surface markers and cytokines/chemokines upon infection withH. ducreyiin vitro. Endogenous interleukin 10 (IL-10) produced by infected MDM downregulated and enhanced expression of several M1 and M2 markers, respectively. Bacterial uptake, mediated mainly by class A scavenger receptors, and activation of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathways were required forH. ducreyi-induced IL-10 production in MDM. Compared to M1 cells, IL-10-polarized M2 cells displayed enhanced phagocytic activity againstH. ducreyiand similar bacterial killing. Thus, IL-10-modulated macrophage polarization may contribute toH. ducreyiclearance during human infection.

scholarly journals Extracts of the Rat Tapeworm, Hymenolepis diminuta, Suppress Macrophage Activation In Vitro and Alleviate Chemically Induced Colitis in Mice

2009 ◽  
Vol 78 (3) ◽  
pp. 1364-1375 ◽  
Author(s):  
M. J. G. Johnston ◽  
A. Wang ◽  
M. E. D. Catarino ◽  
L. Ball ◽  
V. C. Phan ◽  
...  
Keyword(s):  
Inflammatory Disease ◽  
Macrophage Activation ◽  
Peritoneal Macrophages ◽  
Hymenolepis Diminuta ◽  
Poly I:C ◽  
Necrosis Factor Alpha ◽  
Sodium Metaperiodate ◽  
Tnf Α ◽  
The Impact

ABSTRACT Analysis of parasite-host interactions can reveal the intricacies of immunity and identify ways to modulate immunopathological reactions. We assessed the ability of a phosphate-buffered saline-soluble extract of adult Hymenolepis diminuta to suppress macrophage (human THP-1 cell line, murine peritoneal macrophages) activity in vitro and the impact of treating mice with this extract on colitis induced by dinitrobenzene sulfonic acid (DNBS). A high-molecular-mass fraction of adult H. diminuta (HdHMW) or excretory/secretory products reduced macrophage activation: lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) and poly(I:C)-induced TNF-α and IL-6 were suppressed by HdHMW. The active component in the HdHMW extract was minimally sensitive to boiling and trypsin digestion, whereas the use of sodium metaperiodate, as a general deglycosylation strategy, indicated that the immunosuppressive effect of HdHMW was at least partially dependent on a glycan: treating the HdHMW with neuraminidase and α-mannosidase failed to inhibit its blockade of LPS-induced TNF-α production by THP-1 macrophages. Mice treated with DNBS developed colitis, as typified by wasting, shortening of the colon, macroscopic and microscopic tissue damage, and an inflammatory infiltrate. Mice cotreated with HdHMW (three intraperitoneal injections) displayed significantly less inflammatory disease, and this was accompanied by reduced TNF-α production and increased IL-10 and IL-4 production by mitogen-stimulated spleen cells. However, cotreatment of mice with neutralizing anti-IL-10 antibodies had only a minor impact on the anticolitic effect of the HdHMW. We speculate that purification of the immunosuppressive factor(s) from H. diminuta has the potential to lead to the development of novel immunomodulatory drugs to treat inflammatory disease.

scholarly journals A264 HELMINTH-INFECTION MOBILIZES HOST AND MICROBIAL FACTORS THAT CO-OPERATE TO SUPPRESS CHEMICAL-INDUCED COLITIS IN MICE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 141-142
Author(s):  
A J Shute ◽  
B E Callejas Pina ◽  
T S Jayme ◽  
A Wang ◽  
A Buret ◽  
...  
Keyword(s):  
Drinking Water ◽  
Murine Model ◽  
Hymenolepis Diminuta ◽  
Model Systems ◽  
Epithelial Cell Line ◽  
Helminth Parasites ◽  
Critical Determinant ◽  
The Individual ◽  
Helminth Therapy

Abstract Background Infection with helminth parasites suppresses inflammation in murine model systems; for example, IL-10 is important in Hymenolepis diminuta-inhibition of DNBS-induced colitis. Bacteria-derived products can have anti-inflammatory effects. Given that infection with H. diminuta, or other parasitic worms, results in perturbation of the gut microbiota, the present study tested a role for bacteria in helminth-suppression of colitis by assessing reciprocity between IL-10 and butyrate signaling in the amelioration of colitis. Aims To determine if a functional relationship exists between IL-10 and butyrate in the inhibition of colitis observed following infection with the lumen-dwelling tapeworm, Hymenolepis diminuta. Methods Colitis was induced in male BALB/c mice by intra-rectal dinitrobenzene sulphonic acid (DNBS) (3 mg/~22g mouse), with necropsy and assessment 3 days later. Mice received either infection with five H. diminuta cysticercoids by gavage or daily butyrate enemas or acetate in their drinking water. Immunostaining assessed IL-10R protein expression on formalin-fixed sections of colon. The murine IEC4.1 epithelial cell line and epithelial organoids were treated with butyrate and mRNA for the IL10Rα chain assessed, as was colonic tissue from mice. Results Mice infected with H. diminuta or receiving butyrate enemas (n=8–12) were protected from DNBS-induced colitis as gauged by colon length, and macroscopic disease and histopathology scores. Addition of acetate to the drinking water resulted in a more modest anti-colitic effect. Suppression of colitis was accompanied by increased epithelial expression of IL-10 in butyrate- and H. diminuta-treated mice, with the later also showing upregulation of the IL-10R on lamina propria cells; an effect negated by co-treating the mice with broad spectrum antibiotics. In vitro analyses revealed increased IL10Rα mRNA in butyrate-treated epithelia (n=4). Conclusions This study begins to tease apart the host (i.e. IL-10) and bacterial (i.e. butyrate) molecules that mediate H. diminuta-evoked suppression of colitis in a murine model. These proof-of-principle data suggest that knowledge of the individual patient (i.e. immunological basis of their disease and their microbiota) may be a critical determinant of the success or failure of helminth therapy. Funding Agencies CAG, CCCNSERC

Microparticles from apoptotic monocytes induce transient platelet recruitment and tissue factor expression by cultured human vascular endothelial cells via a redox-sensitive mechanism

2007 ◽  
Vol 98 (10) ◽  
pp. 831-837 ◽  
Author(s):  
Sanah Essayagh ◽  
Jean-Marie Xuereb ◽  
Anne-Dominique Terrisse ◽  
Lise Tellier-Cirioni ◽  
Bernard Pipy ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Vascular Endothelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Vascular Endothelial ◽  
Inflammatory Conditions ◽  
Mitogen Activated Protein ◽  
Circulating Microparticles ◽  
Von Willebrand

SummaryCirculating microparticles derived from different types of blood cells have been reported to impair endothelial function and to induce pro-inflammatory and prothrombotic endothelial phenotypes. Although the number of monocyte-derived microparticles (M-MPs) is elevated in the blood of patients with various inflammatory conditions, their interaction with endothelial cells has been poorly investigated so far. In this study, we produced microparticles in vitro from apoptotic human monocytes and examined the effects of their interaction with cultured human umbilical vascular endothelial cells (HUVECs). We found that low concentrations of M-MPs induced the production of reactive oxygen species (ROS), mainly anion superoxide, by the endothelial cells. At sub-toxic concentrations, M-MPs induced a rapid expression of von Willebrand factor at the cell surface, which mediated the transient attachment of non-activated platelets to the endothelium in flow conditions. In parallel, M-MPs up-regulated the expression of functional tissue factor by the endothelial cells. ROS controlled these two major changes and the process involved the phosphorylation of p38 mitogen activated protein kinase. We conclude that M-MPs may contribute to thrombotic events by producing redox signalling in endothelial cells.

Activation of p38 MAP kinase by asbestos in rat mesothelial cells is mediated by oxidative stress

2004 ◽  
Vol 286 (4) ◽  
pp. L859-L865 ◽  
Author(s):  
William A. Swain ◽  
Kenneth J. O'Byrne ◽  
Stephen P. Faux
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Vital Role ◽  
Mesothelial Cells ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Pharmacological Intervention ◽  
Activator Protein 1 ◽  
Sb 203580

Asbestos fibers are biopersistent particles that are capable of stimulating chronic inflammatory responses in the pleura of exposed individuals. Exposure of pleural mesothelial cells, the progenitor cell of malignant mesothelioma, to asbestos induces an array of cellular responses. The present studies investigated whether the p38 mitogen-activated protein kinase cascade was induced under asbestos-exposed conditions. p38 plays a vital role in the response to stressful stimuli and enables the cell to enter an inflammatory state characterized by cytokine production. Western blot and in vitro kinase assays showed increases in dual phosphorylation and actual activity of p38 after exposure to fibrous and nonfibrous (milled) crocidolite; in contrast, polystyrene beads and iron (III) oxide had no such effects. In common with other asbestos-induced events, this was shown to be an oxidative stress-sensitive effect, inasmuch as preincubation with N-acetyl-l-cysteine or α-tocopherol (vitamin E) ameliorated the effect. The present studies show that p38 activity is important for crocidolite-induced activator protein-1 DNA binding, inasmuch as an inhibitor of p38, SB-203580, reduced this activity. Crocidolite-induced cytotoxicity was also reduced with SB-203580, indicating a role for p38 in asbestos-mediated cell death. Our studies suggest that p38 activity could be a crucial factor in the chronic immune response elicited by asbestos and may represent a target for future pharmacological intervention.

scholarly journals p38 mitogen-activated protein kinase activation during platelet storage: consequences for platelet recovery and hemostatic function in vivo

Blood ◽  
2010 ◽  
Vol 115 (9) ◽  
pp. 1835-1842 ◽  
Author(s):  
Matthias Canault ◽  
Daniel Duerschmied ◽  
Alexander Brill ◽  
Lucia Stefanini ◽  
Daphne Schatzberg ◽  
...  
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Platelet Recovery ◽  
Mitochondrial Injury ◽  
Platelet Storage ◽  
Receptor Shedding

AbstractPlatelets undergo several modifications during storage that reduce their posttransfusion survival and functionality. One important feature of these changes, which are known as platelet storage lesion, is the shedding of the surface glycoproteins GPIb-α and GPV. We recently demonstrated that tumor necrosis factor-α converting enzyme (TACE/ADAM17) mediates mitochondrial injury-induced shedding of adhesion receptors and that TACE activity correlates with reduced posttransfusion survival of these cells. We now confirm that TACE mediates receptor shedding and clearance of platelets stored for 16 hours at 37°C or 22°C. We further demonstrate that both storage and mitochondrial injury lead to the phosphorylation of p38 mitogen-activated kinase (MAPK) in platelets and that TACE-mediated receptor shedding from mouse and human platelets requires p38 MAP kinase signaling. Protein kinase C, extracellular regulated-signal kinase MAPK, and caspases were not involved in TACE activation. Both inhibition of p38 MAPK and inactivation of TACE during platelet storage led to a markedly improved posttransfusion recovery and hemostatic function of platelets in mice. p38 MAPK inhibitors had only minor effects on the aggregation of fresh platelets under static or flow conditions in vitro. In summary, our data suggest that inhibition of p38 MAPK or TACE during storage may significantly improve the quality of stored platelets.

scholarly journals In Vivo and In Vitro Characterization of a Novel Neuroprotective Strategy for Stroke: Ischemic Postconditioning

2007 ◽  
Vol 28 (2) ◽  
pp. 232-241 ◽  
Author(s):  
Giuseppe Pignataro ◽  
Robert Meller ◽  
Koichi Inoue ◽  
Andrea N Ordonez ◽  
Michelle D Ashley ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
In Vitro Models ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Neuroprotective Strategy ◽  
The Brain

As clinical trials of pharmacological neuroprotective strategies in stroke have been disappointing, attention has turned to the brain's own endogenous strategies for neuroprotection. Recently, a hypothesis has been offered that modified reperfusion subsequent to a prolonged ischemic episode may also confer ischemic neuroprotection, a phenomenon termed ‘postconditioning’. Here we characterize both in vivo and in vitro models of postconditioning in the brain and offer data suggesting a biological mechanism for protection. Postconditioning treatment reduced infarct volume by up to 50% in vivo and by ∼30% in vitro. A duration of 10 mins of postconditioning ischemia after 10 mins of reperfusion produced the most effective postconditioning condition both in vivo and in vitro. The degree of neuroprotection after postconditioning was equivalent to that observed in models of ischemic preconditioning. However, subjecting the brain to both preconditioning as well as postconditioning did not cause greater protection than each treatment alone. The prosurvival protein kinases extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and Akt show prolonged phosphorylation in the cortex of postconditioned rats. Neuroprotection after postconditioning was inhibited only in the presence of LY294002, which blocks Akt activation, but not U0126 or SB203580, which block ERK and P38 MAP kinase activity. In contrast, preconditioning-induced protection was blocked by LY294002, U0126, and SB203580. Our data suggest that postconditioning may represent a novel neuroprotective approach for focal ischemia/reperfusion, and one that is mediated, at least in part, by the activation of the protein kinase Akt.

scholarly journals Leukotriene B4 is a potent and stereospecific stimulator of neutrophil chemotaxis and adherence

Blood ◽  
1981 ◽  
Vol 58 (3) ◽  
pp. 658-661 ◽  
Author(s):  
J Palmblad ◽  
CL Malmsten ◽  
AM Uden ◽  
O Radmark ◽  
L Engstedt ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Blood Vessels ◽  
Leukotriene B4 ◽  
Optimum Concentration ◽  
Cyclooxygenase Inhibitor ◽  
Neutrophil Chemotaxis ◽  
Leukotriene C4 ◽  
Directed Migration ◽  
High Concentrations

We studied the effects of leukotrienes on in vitro functions of neutrophil polymorphonuclear (PMN) granulocytes. Leukotriene B4 (LTB4) evoked a stimulated and directed migration of neutrophils under agarose with an optimum concentration of 10(-6)M, whereas two nonenzymatically formed isomers (compounds I and II) induced this response at 10(-5)M. Leukotriene C4 (LTC4) and 5-hydroxyeicosate-traenoic acid (5-HETE) did not affect this PMN migration. At the same optimum concentrations, LTB4 and compounds I and II augmented PMN adherence to nylon fibers. The chemotactic and adherence responses were of the same magnitude as with formal-Met-Leu-Phe (fMLP) at 10(-7)M. None of the leukotrienes influenced the spontaneous or phagocytosis-associated chemiluminescence or the ability to kill Staphylococcus aures. The cyclooxygenase inhibitor, indomethacin, inhibited only partly the fMLP-induced migration at high concentrations and stimulated migration at 2.5 x 10(- 7)M, suggesting that arachidonic acid was then mainly metabolized by the lipoxygenase pathways. The lipoxygenase and cyclooxygenase inhibitor, eicosatetraynoic acid, inhibited both spontaneous and stimulated migration at greater or equal to 2.5 x 10(-5)M, but not at lower concentrations. Thus, since LTB4, and to a lesser degree compounds I and II, stimulated migration and adhesion, it is suggested that these mediators could be of importance for the emigration of neutrophils from blood vessels to areas of inflammation.

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