A5002422267- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Dialysis and Renal Disease Management
- Immune cells in cancer
- IL-33, ST2, and ILC Pathways
- Sepsis Diagnosis and Treatment
- Immune Cell Function and Interaction
- Hedgehog Signaling Pathway Studies
- Sphingolipid Metabolism and Signaling
- Nonmelanoma Skin Cancer Studies
- Cell Adhesion Molecules Research
- Antimicrobial Peptides and Activities
- Cytomegalovirus and herpesvirus research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Autoimmune and Inflammatory Disorders Research
- T-cell and B-cell Immunology
- Dermatological and Skeletal Disorders
- Fibroblast Growth Factor Research
- Protein Kinase Regulation and GTPase Signaling
- Cancer Cells and Metastasis
- Genetic and rare skin diseases.
- Kruppel-like factors research
- Monoclonal and Polyclonal Antibodies Research
- Clostridium difficile and Clostridium perfringens research
- Biosimilars and Bioanalytical Methods
Cardiff University
2005-2019
Kidney Research UK
2017
Institute of Infection and Immunity
2011
The University of Tokyo
2007
UConn Health
2002
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
1999
CEA Paris-Saclay
1999
Abstract The successful resolution of inflammation is dependent upon the coordinated transition from initial recruitment neutrophils to a more sustained population mononuclear cells. IL-6, which signals via common receptor subunit gp130, represents crucial checkpoint regulator neutrophil trafficking during inflammatory response by orchestrating chemokine production and leukocyte apoptosis. However, relative contribution specific IL-6-dependent signaling pathways these processes remains...
Highlights•Repeated acute resolving inflammation leads to excessive tissue damage•IL-6 regulates profibrotic IFN-γ-secreting T cells•IFN-γ increases detrimental STAT1 signaling in stromal tissue•STAT1 activity alters homeostatic control of extracellular matrix promote fibrosisSummaryFibrosis response damage or persistent is a pathological hallmark many chronic degenerative diseases. By using model peritoneal inflammation, we have examined how repeated inflammatory activation promotes...
Abstract TLR overactivation may lead to end organ damage and serious acute chronic inflammatory conditions. responses must therefore be tightly regulated control disease outcomes. We show in this study the ability of soluble form TLR2 (sTLR2) regulate proinflammatory responses, demonstrate mechanisms underlying sTLR2 regulatory capacity. Cells overexpressing sTLR2, or stimulated presence protein, are hyporesponsive ligands. Regulation was specific, affected NF-κB activation, phagocytosis,...
The immune system has evolved to sense invading pathogens, control infection, and restore tissue integrity. Despite symptomatic variability in patients, unequivocal evidence that an individual's distinguishes between different organisms mounts appropriate response is lacking. We here used a systematic approach characterize responses microbiologically well-defined infection total of 83 peritoneal dialysis patients on the day presentation with acute peritonitis. A broad range cellular soluble...
Abstract The peritoneal macrophage (Mφ) is the site of greatest 12/15-lipoxygenase (12/15-LOX) expression in mouse; however, its immunoregulatory role this tissue has not been explored. Herein, we show that 12/15-LOX expressed by 95% resident CD11bhigh cells, with remaining 5% being 12/15-LOX−. 12/15-LOX+ cells are phenotypically defined high F4/80, SR-A, and Siglec1 expression, enhanced IL-10 G-CSF generation. In contrast, 12/15-LOX− a dendritic cell population. Resident Mφ numbers were...
Abstract TLR and complement activation ensures efficient clearance of infection. Previous studies documented synergism between TLRs the receptor for pro‐inflammatory peptide C5a (C5aR/CD88), regulation TLR‐induced responses by C5aR, suggesting crosstalk C5aR. However, it is unclear whether how modulate C5a‐induced responses. We demonstrate a marked positive modulatory effect on cell sensitivity to in vitro ex vivo identify an underlying mechanistic target. Pre‐exposure PBMCs whole blood...
Toll-like receptor–mediated responses to pathogens can be modulated by targeting the TLR co-receptor CD14.
Peritoneal dialysis (PD) remains limited by failure due to peritoneal membrane fibrosis driven inflammation caused infections or sterile cellular stress. Given the fundamental role of Toll-like receptors (TLRs) and complement in inflammation, we assessed potential TLR2, TLR4 C5a receptors, C5aR C5L2, as therapeutic targets PD-associated fibrosis. We detected TLR2–, TLR4–, C5aR–mediated proinflammatory fibrotic responses bacteria that were consistent with expression these macrophages (TLR2/4,...
Abstract The antimicrobial responsiveness and function of unconventional human T cells are poorly understood, with only limited access to relevant specimens from sites infection. Peritonitis is a common serious complication in individuals end-stage kidney disease receiving peritoneal dialysis. By analyzing local systemic immune responses dialysis patients presenting acute bacterial peritonitis monitoring before during defined infectious episodes, our data show that Vγ9/Vδ2+ γδ...
Background. Bacterial infection remains a major cause of morbidity and mortality in peritoneal dialysis (PD) patients worldwide. Previous studies have identified key role for mesothelial cells, lining the cavity, coordinating inflammation host defense. Toll-like receptor (TLR) involvement early activation events within mesothelium, however, poorly defined. To investigate initiation bacterial peritonitis, we characterized TLR by ligands human cells (HPMC). Methods. Primary HPMC were isolated...
Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), most common all cancers. These drugs inhibit BCC growth, but they are not curative. Although cells monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern growth with inward differentiation along hair follicle lineages. Most express transcription factor KLF4 and committed to terminal differentiation. A small CD200(+) CD45(-) subpopulation that represents 1.63 ± 1.11%...
Sphingosine 1‐phosphate (S1P), a bioactive lipid mediator, signals via G protein‐coupled receptors (GPCR). The prototypical S1P receptor, 1 (also known as EDG‐1), i ‐linked is critical for vascular maturation during development. Recent work suggested that platelet‐derived growth factor (PDGF)‐induced cell migration required the representing novel mechanism cross‐talk between receptor tyrosine kinases and GPCRs. Since both PDGF are implicated in smooth muscle (VSMC) pathobiology development,...
Pathologies arising as a consequence of human herpesvirus-8 (HHV8) infections are closely associated with the autocrine activity HHV8 encoded IL-6 (vIL-6), which promotes proliferation infected cells and their resistance to apoptosis. In this present report, studies show that vIL-6 may also be important in influencing host's immunological response secondary infections. Using peritoneal inflammation model acute bacterial infection, was found specifically block neutrophil recruitment vivo...
Although the IL-6-related cytokine oncostatin M (OSM) affects processes associated with disease progression, specific function of OSM in face an inflammatory challenge remains unclear. In this report, a peritoneal model acute inflammation was used to define influence on chemokine-mediated leukocyte recruitment. When compared wild-type and IL-6-deficient mice, receptor-beta-deficient (OSMR-KO) mice resulted enhanced monocytic cell trafficking. contrast OSMR-KO displayed no difference...
Early upregulation of receptor-interacting protein-2 (RIP2) expression during peritoneal dialysis (PD)-associated peritonitis correlates with a favorable clinical outcome, while failure to upregulate RIP2 protracted course. We noticed that patients who do not PD-associated have more macrophages the early phase infection.To study mechanism behind this observation, we examined role in immune response bacterial challenge mouse model acute peritonitis. injected RIP2(+/+) and RIP2(-/-) mice...
Peritoneal dialysis (PD) is a life-sustaining kidney replacement therapy for the increasing number of people with permanent failure across all age groups worldwide. Although PD potentially offers socioeconomic and performance benefits over hemodialysis, both treatments severely accelerate complications chronic disease, in particular atherosclerotic disease progression that worsens outcomes when compared non-dialysis patients.1 Improved understanding underlying molecular pathogenic mechanisms...