A5039339360- Immune Response and Inflammation
- Inflammatory mediators and NSAID effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Adenosine and Purinergic Signaling
- Cell Adhesion Molecules Research
- Receptor Mechanisms and Signaling
- Systemic Lupus Erythematosus Research
- Adipose Tissue and Metabolism
- Asthma and respiratory diseases
- S100 Proteins and Annexins
- Gout, Hyperuricemia, Uric Acid
- Endometriosis Research and Treatment
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Neuropeptides and Animal Physiology
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Eicosanoids and Hypertension Pharmacology
- Neuroinflammation and Neurodegeneration Mechanisms
- Cytokine Signaling Pathways and Interactions
- Endometrial and Cervical Cancer Treatments
- Chemokine receptors and signaling
- Estrogen and related hormone effects
- NF-κB Signaling Pathways
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
Université Laval
2014-2025
Cégep de Sherbrooke
2025
Centre hospitalier de l'Université Laval
2005-2024
Trinity College Dublin
2022
Centre hospitalier universitaire de Québec
1993-2021
Harvard University
1999-2001
Brigham and Women's Hospital
1999-2001
University of Southern California
1999-2000
Boston University
2000
Royal Adelaide Hospital
1997-1998
Significance On activation, blood platelets package components from their cytoplasm into microparticles (MPs), tiny vesicles released by cytoplasmic membrane budding and shedding. Given that MPs can impact other cellular lineages on internalization, we aimed to decipher the mechanisms promoting MP internalization recipients. We modeled neutrophils identified a predominant lipid, 12(S)-hydroxyeicosatetranoic acid, as mediator critical for promotion of internalization. were found inside...
Real-time polymerase chain reaction (PCR) constitutes a significant improvement over traditional end-point PCR, as it allows the quantification of starting amounts nucleic acid templates, in real-time. However, requires validation through numerous internal controls and standard curves. We describe this paper simple protocol which uses real-time PCR to compare mRNA levels gene interest between different experimental conditions. Comparative can be relatively low-cost method does not require...
The potential involvement of the inducible cyclooxygenase isoform (COX-2) and role novel lipid mediators were investigated in pathogenesis periodontal disease. Crevicular fluids from localized juvenile periodontitis (LJP) patients contained prostaglandin (PG)E2 5-lipoxygenase-derived products, leukotriene B4, biosynthesis interaction product, lipoxin (LX)A4. Neutrophils peripheral blood LJP patients, but not asymptomatic donors, also generated LXA4, suggesting a for this immunomodulatory...
The impact of lipoxin A4 (LXA4) and aspirin-triggered lipoxins (ATLs) was investigated in tumor necrosis factor (TNF)-α–initiated neutrophil (polymorphonuclear leukocyte) responses vitro vivo using metabolically stable LX analogues. At concentrations as low 1–10 nM, the LXA4 ATL analogues each inhibited TNF-α–stimulated superoxide anion generation IL-1β release by human polymorphonuclear leukocytes. These LXA4-ATL actions were time concentration dependent proved selective for TNF-α, these...
The accumulation of DNA and nuclear components in blood their recognition by autoantibodies play a central role the pathophysiology systemic lupus erythematosus (SLE). Despite efforts, sources circulating autoantigens SLE are still unclear. Here, we show that SLE, platelets release mitochondrial DNA, majority which is associated with extracellular organelle. Mitochondrial patients correlates platelet degranulation. This process requires stimulation FcγRIIA, receptor for immune complexes....
Background. Toll-like receptors (TLRs) play an important role in the innate immune response to pathogens. TLR8 has been found recognize RNA derived from various viruses, including human immunodeficiency virus (HIV). Presently, very little is known about influence of genetic variation on susceptibility and progression HIV disease. Methods results. We genotyped a population 782 HIV-positive adults 550 healthy control subjects for 3 nonsynonymous single-nucleotide polymorphisms. that presence...
Proinflammatory agents were assessed for their capacity to stimulate the expression of inducible cyclooxygenase isoform (COX-2) in human neutrophils. A number agents, including PMA, opsonized bacteria and zymosan, LPS, GM-CSF, TNF-α, fMLP, induced COX-2 protein through signaling pathways involving transcription synthesis events. Northern blots showed that freshly isolated neutrophils expressed low levels mRNA, which rapidly increased after incubation with inflammatory agents....
In LPS-stimulated human neutrophils, engagement of the adenosine A2A receptor selectively prevented expression and release TNF-alpha, MIP-1alpha/CCL3, MIP-1beta/CCL4, MIP-2alpha/CXCL2, MIP-3alpha/CCL20. mice lacking receptor, granulocytes that migrated into air pouch 4 h after LPS injection expressed higher mRNA levels MIP-1alpha, MIP-1beta than PMNs from wild-type mice. mononuclear cells present in 72 injection, IL-1beta, IL-6, MCP-2/CCL6 was A2AR knockout addition to highlighting...
Abstract Synthesis of TNF-alpha and IL-1beta, by monocytes/macrophages can be partially regulated the eicosanoid, PGE2. We report here that inhibition both PGE2 thromboxane A2 (TXA2) synthesis a prostaglandin H synthase inhibitor, NS-398, had no effect on either or even though addition to these treated cells dose-dependently inhibited IL-1beta synthesis. Because TXA2 is major eicosanoid product stimulated human monocytes, we examined its influence cytokine production. Inhibition...
The distribution of cytosolic phospholipase A 2 (cPLA ), arachidonate 5–lipoxygenase, and 5–lipoxygenase‐activating protein (5–LAP) was investigated in subcellular fractions human neutrophils disrupted by three techniques. As determined immunoblot analysis, the bulk cPLA2 5–lipoxygenase detected unstimulated sonication or cavitation. After cell stimulation with calcium ionophore A23187, both proteins accumulated primarily nuclei‐containing fractions; this accumulation accompanied a loss...
The nociceptin receptor (Noci-R) is a G protein-coupled present in neural tissues and its activation by involved the processing of pain signals. Here, we report that Noci-R functional on peripheral blood polymorphonuclear leukocytes (PMN). Human PMN express mRNA for Noci-R, nucleotide sequence determined, specific binding with [(125)I]-labeled gave an apparent K(d) approximately 1.5 nM this opioid receptor. Nociceptin evoked chemotaxis maximal activity at 100 pM, without intracellular Ca(2+)...
The synthesis of leukotrienes in human blood neutrophils chiefly relies on the activity two enzymes, phospholipase A2 and 5-lipoxygenase (5-LO). In turn, activation 5-LO requires participation a recently characterized membrane-bound protein, 5-LO-activating protein (FLAP). this study, we have investigated conditions under which FLAP expression may be modulated. Of several cytokines tested, only granulocyte/macrophage colony-stimulating factor (GM-CSF) (and to lesser extent tumor necrosis...
Abstract Prostaglandin endoperoxide synthase (PGHS; cyclooxygenase), the rate-limiting enzyme in conversion of arachidonic acid to prostanoids, has two isoforms. PGHS-1 is constitutively expressed and involved homeostasis, whereas PGHS-2 inducible monocytes response proinflammatory agents. Using freshly elutriated human monocytes, we examined effect on expression certain cytokine-suppressive anti-inflammatory drugs such as SK&F 86002. Incubation with serum-treated zymosan (STZ)...
Nociceptin is a neuropeptide sharing sequence homology with classical opioid peptides but distinct pharmacological profile. Through activation of its receptor, NociR, nociceptin has been linked several physiological functions in the central nervous system including memory, locomotion, and processing pain signals. Recently, peripheral blood neutrophils (PMNs) were demonstrated to express functional result suggesting that additional remain be elucidated. The present study investigated...
Abstract Polymorphonuclear neutrophils (granulocytes; PMNs) are often the first blood cells to migrate toward inflammatory lesions perform host defense functions. PMNs respond specific stimuli by releasing several factors and generate lipid mediators of inflammation from 5-lipoxygenase inducible cyclooxygenase (COX)-2 pathways. In view adenosine’s anti-inflammatory properties suppressive impact on pathway, we addressed in this study autacoid COX-2 pathway. We observed that adenosine...
ABSTRACT Toll‐like receptors (TLR) recognize pathogen‐associated molecular patterns and play important roles in the innate immune system. While single‐stranded viral RNA is natural ligand of TLR7/TLR8, imidazoquinoline resiquimod (R‐848) recognized as a potent synthetic agonist TLR7/TLR8. We investigated effects TLR7/8 activation on lipid mediator production polymorphonuclear leukocytes exposed to R‐848. Although R‐848 had minimal by itself, it strongly enhanced leukotriene B 4 formation...
Stimulation of human polymorphonuclear leukocytes (PMNL) with granulocyte-macrophage CSF (GM-CSF) results in the enhanced expression several genes, including some coding for cytokines and enzymes. In this study, we investigated ability GM-CSF to up-regulate neutrophil 5-lipoxygenase (5-LO), a key enzyme leukotriene synthetic pathway. induced dose- time-dependent de novo synthesis 5-LO PMNL, as determined by immunoprecipitation 35S-methionine-labeled 5-LO. This up-regulation occurred within...
Hypoxia occurs during a number of conditions in which altered epithelial proliferation is critical, including tumor development. Microarray analysis colon-derived cells revealed hypoxia-dependent increase the expression amphiregulin, an EGF receptor (EGFR) ligand that activates and has been associated with development colonic tumors. Amphiregulin was also induced tissues from mice exposed to whole animal hypoxia. The hypoxic upregulation amphiregulin independent classic transcriptional...
Neutrophils, which are often the first to migrate at inflamed sites, can generate leukotriene B4 from 5-lipoxygenase pathway and prostaglandin E2 through inducible cyclooxygenase-2 pathway. Adenosine, an endogenous autacoid with several anti-inflammatory properties, blocks synthesis of while it potentiates in fMLP-treated neutrophils, following activation A2A receptor. Using murine air pouch model inflammation, we observed that inflammatory leukocytes mice lacking receptor have less...