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https://www.readbyqxmd.com/read/26408663/cooperation-between-il-7-receptor-and-integrin-%C3%AE-2%C3%AE-1-cd49b-drives-th17-mediated-bone-loss
#1
Mohammed-Amine El Azreq, Claudie Arseneault, Marc Boisvert, Nathalie Pagé, Isabelle Allaeys, Patrice E Poubelle, Philippe A Tessier, Fawzi Aoudjit
Th17 cells are critical effectors in inflammation and tissue damage such as bone erosion, but the mechanisms regulating their activation in this process are not fully understood. In this study, we considered the cooperation between cytokine receptors and integrin pathways in Th17-osteoclast function. We found that human Th17 cells coexpress IL-7R and the collagen-binding integrin α2β1 (CD49b), and IL-7 increases their adhesion to collagen via α2β1 integrin. In addition, coengagement of the two receptors in human Th17 cells cooperatively enhanced their IL-17 production and their osteoclastogenic function...
November 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/26106157/platelet-microparticles-are-internalized-in-neutrophils-via-the-concerted-activity-of-12-lipoxygenase-and-secreted-phospholipase-a2-iia
#2
Anne-Claire Duchez, Luc H Boudreau, Gajendra S Naika, James Bollinger, Clémence Belleannée, Nathalie Cloutier, Benoit Laffont, Raifish E Mendoza-Villarroel, Tania Lévesque, Emmanuelle Rollet-Labelle, Matthieu Rousseau, Isabelle Allaeys, Jacques J Tremblay, Patrice E Poubelle, Gérard Lambeau, Marc Pouliot, Patrick Provost, Denis Soulet, Michael H Gelb, Eric Boilard
Platelets are anucleated blood elements highly potent at generating extracellular vesicles (EVs) called microparticles (MPs). Whereas EVs are accepted as an important means of intercellular communication, the mechanisms underlying platelet MP internalization in recipient cells are poorly understood. Our lipidomic analyses identified 12(S)-hydroxyeicosatetranoic acid [12(S)-HETE] as the predominant eicosanoid generated by MPs. Mechanistically, 12(S)-HETE is produced through the concerted activity of secreted phospholipase A2 IIA (sPLA2-IIA), present in inflammatory fluids, and platelet-type 12-lipoxygenase (12-LO), expressed by platelet MPs...
July 7, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25982332/a-transgenic-mouse-model-for-the-in-vivo-bioluminescence-imaging-of-the-expression-of-the-lysophosphatidic-acid-receptor-3-relevance-for-inflammation-and-uterine-physiology-research
#3
Chenqi Zhao, Anne Sardella, Lynn Davis, Patrice E Poubelle, Sylvain G Bourgoin, Maria J Fernandes
Lysophosphatidic acid (LPA) is a lipid-derived signaling molecule that plays key roles in diverse biological processes including inflammation and uterine remodeling. Although the function of LPA and its receptors has been extensively studied using knock-out mice, the temporal-spatial expression of LPA receptors is less well-characterized. To gain further insight into the dynamic regulation of LPA receptor 3 (Lpar3) expression in vivo by bioluminescence imaging, we generated and characterized mice transgenic for a putative Lpar3 promoter fragment...
August 2015: Transgenic Research
https://www.readbyqxmd.com/read/25275312/il-32%C3%AE-delays-spontaneous-apoptosis-of-human-neutrophils-through-mcl-1-regulated-primarily-by-the-p38-mapk-pathway
#4
Isabelle Allaeys, Irina Gymninova, Charlotte Canet-Jourdan, Patrice E Poubelle
IL-32γ is a multifunctional cytokine involved in various inflammatory and auto-immune diseases in which neutrophils can affect the evolution of these diseases. To persist at inflammatory sites, neutrophils require inhibition of their rapid and constitutive apoptosis, an inhibitory effect that phlogogenic cytokines support. To date, the effects of IL-32γ on neutrophils remain unknown. We demonstrate that IL-32γ delays, in a dose-dependent manner, the spontaneous apoptosis of human blood neutrophils by activating mainly p38 MAPK through rapid p38 phosphorylation...
2014: PloS One
https://www.readbyqxmd.com/read/25128082/a-tagged-parathyroid-hormone-derivative-as-a-carrier-of-antibody-cargoes-transported-by-the-g-protein-coupled-pth1-receptor
#5
Xavier Charest-Morin, Jean-Philippe Fortin, Robert Lodge, Isabelle Allaeys, Patrice E Poubelle, François Marceau
Based on the known fact that the parathyroid hormone (PTH) might be extended at its C-terminus with biotechnological protein cargoes, a vector directing the secretion of PTH1-84 C-terminally fused with the antigenic epitope myc (PTH-myc) was exploited. The functional properties and potential of this analog for imaging PTH1R-expressing cells were examined. The PTH-myc construct was recombinantly produced as a conditioned medium (CM) of transfected HEK 293a cells (typical concentrations of 187nM estimated with ELISAs for PTH)...
October 2014: Peptides
https://www.readbyqxmd.com/read/24792438/lysophosphatidic-acid-induced-il-8-secretion-involves-msk1-and-msk2-mediated-activation-of-creb1-in-human-fibroblast-like-synoviocytes
#6
Chenqi Zhao, Weili Hui, Maria J Fernandes, Patrice E Poubelle, Sylvain G Bourgoin
Lysophosphatidic acid (LPA) is a pleiotropic lipid mediator that promotes motility, survival, and the synthesis of chemokines/cytokines such as interleukin-8 (IL-8) and interleukin-6 by human fibroblast-like synoviocytes from patients with rheumatoid arthritis (RAFLS). In those cells LPA was reported to induce IL-8 secretion through activation of various signaling pathways including p38 mitogen-activated protein kinase (p38 MAPK), p42/44 MAPK, and Rho kinase. In addition to those pathways we report that mitogen- and stress-activated protein kinases (MSKs) known to be activated downstream of the ERK1/2 and p38 MAPK cascades and CREB are phosphorylated in response to LPA...
July 1, 2014: Biochemical Pharmacology
https://www.readbyqxmd.com/read/24456929/nlrp3-promotes-autophagy-of-urate-crystals-phagocytized-by-human-osteoblasts
#7
Isabelle Allaeys, François Marceau, Patrice E Poubelle
INTRODUCTION: Monosodium urate (MSU) microcrystals present in bone tissues of chronic gout can be ingested by nonprofessional phagocytes like osteoblasts (OBs) that express NLRP3 (nucleotide-binding domain and leucine-rich repeat region containing family of receptor protein 3). MSU is known to activate NLRP3 inflammasomes in professional phagocytes. We have identified a new role for NLRP3 coupled to autophagy in MSU-stimulated human OBs. METHODS: Normal human OBs cultured in vitro were investigated for their capacity for phagocytosis of MSU microcrystals by using confocal microscopy...
November 1, 2013: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/24244022/%C3%AE-2%C3%AE-1-integrin-regulates-th17-cell-activity-and-its-neutralization-decreases-the-severity-of-collagen-induced-arthritis
#8
Mohammed-Amine El Azreq, Marc Boisvert, Annabelle Cesaro, Nathalie Pagé, Lionel Loubaki, Isabelle Allaeys, Jamila Chakir, Patrice E Poubelle, Philippe A Tessier, Fawzi Aoudjit
Th17 cells play a critical role in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms by which these cells regulate the development of RA are not fully understood. We have recently shown that α2β1 integrin, the receptor of type I collagen, is the major collagen-binding integrin expressed by human Th17 cells. In this study, we examined the role of α2β1 integrin in Th17-mediated destructive arthritis in the murine model of collagen-induced arthritis (CIA). We found that α2β1 integrin is expressed on synovial Th17 cells from CIA mice and its neutralization with a specific mAb significantly reduced inflammation and cartilage degradation, and protected the mice from bone erosion...
December 15, 2013: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/24189030/picea-mariana-polyphenolic-extract-inhibits-phlogogenic-mediators-produced-by-tnf-%C3%AE-activated-psoriatic-keratinocytes-impact-on-nf-%C3%AE%C2%BAb-pathway
#9
Martha-Estrella García-Pérez, Isabelle Allaeys, Daniel Rusu, Roxane Pouliot, Tatjana Stevanovic Janezic, Patrice E Poubelle
ETHNOPHARMACOLOGICAL RELEVANCE: Picea mariana ((Miller) Britton, Sterns, and Poggenburg; Pinaceae) bark has been traditionally used by North American natives for treating topical inflammations. It has been also suggested to improve various inflammatory skin disorders like Psoriasis vulgaris. Extracts from this bark storage protein contain polyphenolic compounds which have well-known antiinflammatory activities. Based on the capacity of polyphenolic compounds to modulate functions of normal human keratinocytes, this study was set up to decipher the mechanisms of action of a chemically characterized polyphenolic extract from Picea mariana bark (BS-EAcf) on lesional keratinocytes of skin with psoriasis vulgaris, a disease driven by the immune system in which TNF-α plays a significant role...
2014: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/23974213/psoriatic-keratinocytes-prime-neutrophils-for-an-overproduction-of-superoxide-anions
#10
Simon Guérard, Isabelle Allaeys, Guillaume Martin, Roxane Pouliot, Patrice E Poubelle
Psoriatic plaques result from an abnormal proliferation of keratinocytes associated with the local presence of T lymphocytes and neutrophils. The exact role of neutrophils in psoriatic lesions remains unclear. The present investigation was aimed at deciphering the capacity of psoriatic keratinocytes to alter in vitro functions of neutrophils. Blood neutrophils from healthy donors were incubated with psoriatic (PK) or healthy keratinocytes (HK) with and without IL-2-activated healthy T lymphocytes. The study was focussed on neutrophil capacity of adherence, viability and superoxide anion production...
December 2013: Archives of Dermatological Research
https://www.readbyqxmd.com/read/23902799/cross-linking-of-iggs-bound-on-circulating-neutrophils-leads-to-an-activation-of-endothelial-cells-possible-role-of-rheumatoid-factors-in-rheumatoid-arthritis-associated-vascular-dysfunction
#11
Emmanuelle Rollet-Labelle, Myriam Vaillancourt, Louis Marois, Marianna M Newkirk, Patrice E Poubelle, Paul H Naccache
BACKGROUND: Rheumatoid arthritis is characterized by the presence of circulating auto-antibodies, including rheumatoid factors, which recognize the Fc portion of IgGs. The neutrophil is the most abundant circulating leukocyte and it expresses high levels of FcγRs on its surface. The aim of the present study was to examine the capacity of circulating human neutrophils to be activated by rheumatoid factors and the consequences of these events on endothelium. METHODS: Neutrophil-bound IgGs were cross-linked with anti-human IgGs to mimick the presence of circulating rheumatoid factors and FcγRs-dependent signalling events and functions were examined...
2013: Journal of Inflammation
https://www.readbyqxmd.com/read/23838833/new-therapies-under-development-for-psoriasis-treatment
#12
REVIEW
Martha-Estrella García-Pérez, Tatjana Stevanovic, Patrice E Poubelle
PURPOSE OF REVIEW: An improved understanding of the psoriasis pathogenesis has provided new insights into potential new therapeutic targets, which has positively influenced the development of novel therapies. This monograph reviews recent clinical trials concerning new small molecules and biotech products under investigation for plaque psoriasis treatment. Emphasis is placed on mechanism of action, efficacy and adverse effects of these new agents. RECENT FINDINGS: Recent literature has shown that there are several new drugs under development for psoriasis treatment including new A3 adenosine receptor agonists, biologics like anti-tumor necrosis factor, anti-interleukin-17, anti-interleukin-12/23 and anti-interleukin-17 receptor agents, as well as Janus kinase and phosphodiesterase 4 inhibitors, among others...
August 2013: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/22525430/pathological-crosstalk-in-vitro-between-t-lymphocytes-and-lesional-keratinocytes-in-psoriasis-necessity-of-direct-cell-to-cell-contact
#13
Guillaume Martin, Simon Guérard, Marie-Michèle Rosa Fortin, Daniel Rusu, Jacques Soucy, Patrice E Poubelle, Roxane Pouliot
Psoriasis, a chronic autoimmune-related skin disease, involves both immune and non-immune cells like T cells and keratinocytes. This study investigates the regulatory role of T cells-keratinocyte interactions during psoriasis on immune factors production. Cytokines and chemokines were evaluated by multiplex and ELISA assays in an in vitro model of co-culture of keratinocytes with T lymphocytes. Keratinocytes were from psoriatic skin lesions or healthy skin. T lymphocytes were from healthy volunteers. Psoriatic keratinocytes (PKs) alone generated concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-8, monocyte chemotactic protein (MCP)-1, interferon-γ-induced protein 10 kDa (IP-10) and vascular endothelial growth factor (VEGF) higher than those produced by healthy keratinocytes (HKs)...
July 2012: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/21521824/tnf-alpha-promotes-lpa1-and-lpa3-mediated-recruitment-of-leukocytes-in-vivo-through-cxcr2-ligand-chemokines
#14
Chenqi Zhao, Anne Sardella, Jerold Chun, Patrice E Poubelle, Maria J Fernandes, Sylvain G Bourgoin
Lysophosphatidic acid (LPA) is a bioactive lysophospholipid present in low concentrations in serum and biological fluids but in high concentrations at sites of inflammation. LPA evokes a variety of cellular responses via binding to and activation of its specific G protein-coupled receptors (GPCR), namely LPA(1-6). Even though LPA is a chemoattractant for inflammatory cells in vitro, such a role for LPA in vivo remains largely unexplored. In the present study, we used the murine air pouch model to study LPA-mediated leukocyte recruitment in vivo using selective LPA receptor agonist/antagonist and LPA(3)-deficient mice...
July 2011: Journal of Lipid Research
https://www.readbyqxmd.com/read/21403645/osteoblast-retraction-induced-by-adherent-neutrophils-promotes-osteoclast-bone-resorption-implication-for-altered-bone-remodeling-in-chronic-gout
#15
Isabelle Allaeys, Daniel Rusu, Sylvain Picard, Marc Pouliot, Pierre Borgeat, Patrice E Poubelle
Bone destruction in chronic gout is correlated with deposits of monosodium urate (MSU) crystals. Bone with MSU tophi were histopathologically shown to have altered remodeling and cellular distribution. We investigated the impact of neutrophils in bone remodeling associated with MSU and demonstrated that neutrophils, through elastase localized at their surface, induced retraction of confluent osteoblasts (OBs) previously layered on calcified matrix. This OB retraction allowed osteoclasts to resorb cell-free areas of the matrix...
June 2011: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/20522834/scaffold-guided-subchondral-bone-repair-implication-of-neutrophils-and-alternatively-activated-arginase-1-macrophages
#16
Caroline D Hoemann, Gaoping Chen, Catherine Marchand, Nicolas Tran-Khanh, Marc Thibault, Anik Chevrier, Jun Sun, Matthew S Shive, Maria J G Fernandes, Patrice E Poubelle, Michael Centola, Hani El-Gabalawy
BACKGROUND: Microfracture and drilling elicit a cartilage repair whose quality depends on subchondral bone repair. Alternatively activated (AA) macrophages express arginase-1, release angiogenic factors, and could be potential mediators of trabecular bone repair. HYPOTHESIS: Chitosan-glycerol phosphate (GP)/blood implants elicit arginase-1+ macrophages in vivo through neutrophil-dependent mechanisms and improve trabecular bone repair of drilled defects compared with drilling alone...
September 2010: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/20032479/a-bovine-whey-protein-extract-stimulates-human-neutrophils-to-generate-bioactive-il-1ra-through-a-nf-kappab-and-mapk-dependent-mechanism
#17
Daniel Rusu, Réjean Drouin, Yves Pouliot, Sylvie Gauthier, Patrice E Poubelle
Innate immunity depends on the efficiency of neutrophils to be activated rapidly to restore homeostasis. It can benefit from priming agents that enhance neutrophil capacity to respond more efficiently to a subsequent stimulation. Among natural products, a bovine whey protein extract (WPE) has been shown to prime normal human blood neutrophils by enhancing their chemotaxis, phagocytosis, oxidative burst, and degranulation. These leukocytes are also an important source of cytokines, some of which have antiinflammatory functions...
February 2010: Journal of Nutrition
https://www.readbyqxmd.com/read/19854263/pkc-delta-controls-the-fmlf-induced-overproduction-of-superoxide-by-neutrophils
#18
Catherine Matron, Arpita Chakravarti, Isabelle Allaeys, Patrice E Poubelle
Antimicrobial defense by neutrophils implicates the production of reactive oxygen species. Neutrophil responses can be modulated by agonists such as bacterial peptides and proinflammatory factors that modulate neutrophil activity and survival. We evaluated the production of superoxide anions (O(2)(-)) in response to fMLF by normal human neutrophils after 3 days of preincubation with GM-CSF + IL-4 + TNF-alpha (survival medium). After 3 days of incubation in survival medium, long-lived neutrophils produced up to six times more O(2)(-) relative to control neutrophils in response to fMLF and WKYMVM...
January 15, 2010: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/19636293/reprogramming-of-a-subpopulation-of-human-blood-neutrophils-by-prolonged-exposure-to-cytokines
#19
Arpita Chakravarti, Daniel Rusu, Nicolas Flamand, Pierre Borgeat, Patrice E Poubelle
Essential cells of innate immunity, neutrophils are often considered to be a homogenous population of terminally differentiated cells. During inflammation, neutrophils are extravasated cells exposed to local factors that prolong their survival and activate their production of mediators implicated in disease progression. In this study, a phenotypically distinct subset of human neutrophils that appear after prolonged exposure to cytokines was characterized. Freshly isolated neutrophils from healthy donors were incubated with granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha and interleukin (IL)-4, three cytokines that are locally present in various inflammatory conditions...
October 2009: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/19594752/intracellular-sequestration-of-amiodarone-role-of-vacuolar-atpase-and-macroautophagic-transition-of-the-resulting-vacuolar-cytopathology
#20
G Morissette, A Ammoury, D Rusu, M C Marguery, R Lodge, P E Poubelle, F Marceau
BACKGROUND AND PURPOSE: Tissue deposits of the anti-arrhythmic drug amiodarone are a major source of side effects (skin discoloration, etc.). We addressed the mechanism of the concentration of amiodarone in cells, and characterized the resulting vacuolar cytopathology and its evolution towards macroautophagy. EXPERIMENTAL APPROACH: Sequestration of amiodarone in human cells (macrophages, smooth muscle cells, HEK 293a cells) was evaluated using its violet fluorescence and cytopathology using GFP-conjugated subcellular markers...
August 2009: British Journal of Pharmacology
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