Unlabelled: Host-microbe interactions that facilitate entry into mammalian cells are essential for obligate intracellular bacterial survival and pathogenesis. is an obligate intracellular bacterium that invades neutrophils to cause granulocytic anaplasmosis. The invasin-receptor pairs and signaling events that induce uptake are inadequately defined.
View Article and Find Full Text PDFImplanted medical devices, from artificial heart valves and arthroscopic joints to implantable sensors, often induce a foreign body response (FBR), a form of chronic inflammation resulting from the inflammatory reaction to a persistent foreign stimulus. The FBR is characterized by a subset of multinucleated giant cells (MGCs) formed by macrophage fusion, the foreign body giant cells (FBGCs), accompanied by inflammatory cytokines, matrix deposition, and eventually deleterious fibrotic implant encapsulation. Despite efforts to improve biocompatibility, implant-induced FBR persists, compromising the utility of devices and making efforts to control the FBR imperative for long-term function.
View Article and Find Full Text PDFBacterial pigments represent a diverse group of secondary metabolites, which confer fitness advantages to the producers while residing in communities. The bioactive potential of such metabolites, including antimicrobial, anticancer, and immunomodulation, are being explored. Reckoning that a majority of such pigments are produced in response to quorum sensing (QS) mediated expression of biosynthetic gene clusters and, in turn, influence cell-cell communication, systemic profiling of the pigments for possible impact on QS appears crucial.
View Article and Find Full Text PDFProteoglycan 4 (PRG4, lubricin) is a mucin-like glycoprotein present on the ocular surface that has both boundary lubricating and anti-inflammatory properties. Full-length recombinant human PRG4 (rhPRG4) has been shown to be clinically effective in improving signs and symptoms of dry eye disease (DED). In vitro, rhPRG4 has been shown to reduce inflammation-induced cytokine production and NFκB activity in corneal epithelial cells, as well as to bind to and inhibit MMP-9 activity.
View Article and Find Full Text PDFBone regeneration depends on a pool of bone/cartilage stem/progenitor cells and signaling mechanisms regulating their differentiation. Using in vitro approach, we have shown that PDGF signaling through PDGFRβ inhibits BMP2-induced osteogenesis, and significantly attenuates expression of BMP2 target genes. We evaluated outcomes of treatment with two anabolic agents, PDGF and BMP2 using different bone healing models.
View Article and Find Full Text PDFDry Eye Disease (DED) is a complex pathology affecting millions of people with significant impact on quality of life. Corneal inflammation, including via the nuclear factor kappa B (NFκB) pathway, plays a key etiological role in DED. Recombinant human proteoglycan 4 (rhPRG4) has been shown to be a clinically effective treatment for DED that has anti-inflammatory effects in corneal epithelial cells, but the underlying mechanism is still not understood.
View Article and Find Full Text PDFDry eye disease (DED) affects hundreds of millions of people worldwide. It is characterized by the production of inflammatory cytokines and chemokines as well as damaging matrix metalloproteinases (MMPs) at the ocular surface. While proteoglycan 4 (PRG4), a mucin-like glycoprotein present at the ocular surface, is most well known as a boundary lubricant that contributes to ocular surface integrity, it has been shown to blunt inflammation in various cell types, suggesting a dual mechanism of action.
View Article and Find Full Text PDFThe transmembrane aminopeptidase CD13 is highly expressed in cells of the myeloid lineage, regulates dynamin-dependent receptor endocytosis and recycling and is a necessary component of actin cytoskeletal organization. Here, we show that CD13-deficient mice present a low bone density phenotype with increased numbers of osteoclasts per bone surface, but display a normal distribution of osteoclast progenitor populations in the bone marrow and periphery. In addition, the bone formation and mineral apposition rates are similar between genotypes, indicating a defect in osteoclast-specific function in vivo.
View Article and Find Full Text PDFThe Coronaviridae family includes the seven known human coronaviruses (CoV) that cause mild to moderate respiratory infections (HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1) as well as severe illness and death (MERS-CoV, SARS-CoV, SARS-CoV-2). Severe infections induce hyperinflammatory responses that are often intensified by host adaptive immune pathways to profoundly advance disease severity. Proinflammatory responses are triggered by CoV entry mediated by host cell surface receptors.
View Article and Find Full Text PDFMol Cell Oncol
August 2019
Membrane recycling is critical to numerous cell functions and its dysregulation contributes to cancer and metastasis. We established that activation of the transmembrane molecule aminopeptidase N (ANPEP, also known as CD13) tethers the IQ motif containing, guanosine triphosphate hydrolase activating protein 1 (IQGAP1) scaffolding protein at the plasma membrane, thus stimulating the recycling regulator ADP-ribosylation factor 6 (ARF6) to ensure proper recycling of β1-integrin and other membrane components impacting cell attachment.
View Article and Find Full Text PDFBackground And Aims: Atherosclerosis is an inflammatory cardiovascular disorder characterized by accumulation of lipid-loaded macrophages in the intima. Prolonged accumulation leads to apoptosis of macrophages and eventually to progression of lesion development. Prevention of macrophage accumulation within the intima has been shown to reduce lesion formation.
View Article and Find Full Text PDFCell attachment to the extracellular matrix (ECM) requires a balance between integrin internalization and recycling to the surface that is mediated by numerous proteins, emphasizing the complexity of these processes. Upon ligand binding in various cells, the β1 integrin is internalized, traffics to early endosomes, and is returned to the plasma membrane through recycling endosomes. This trafficking process depends on the cyclical activation and inactivation of small guanosine triphosphatases (GTPases) by their specific guanine exchange factors (GEFs) and their GTPase-activating proteins (GAPs).
View Article and Find Full Text PDFSphingosine Kinase-2 (Sphk2) is responsible for the production of the bioactive lipid Sphingosine-1 Phosphate, a key regulator of tissue repair. Here we address the in vivo significance of Sphingosine Kinase -2 in renal inflammation/fibrosis in response to unilateral ureteral obstruction using both genetic and pharmacological strategies. Obstructed kidneys of Sphk2-/- mice showed reduced renal damage and diminished levels of the renal injury markers TGFβ1 and αSMA when compared to wild type controls.
View Article and Find Full Text PDFProstate-specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase expressed in a number of tissues. PSMA participates in various biological functions depending on the substrate available in the particular tissue; in the brain, PSMA cleaves the abundant neuropeptide N-acetyl-aspartyl-glutamate to regulate release of key neurotransmitters, while intestinal PSMA cleaves polyglutamated peptides to supply dietary folate. PSMA expression is also progressively upregulated in prostate cancer where it correlates with tumor progression as well as in tumor vasculature, where it regulates angiogenesis.
View Article and Find Full Text PDFThe aim of this study was to investigate pharmaceutical potentialities of a polymeric microparticulate drug delivery system for modulating the drug profile of poorly water-soluble quercetin. In this research work two cost effective polymers sodium alginate and chitosan were used for entrapping the model drug quercetin through ionic cross linking method. In vitro drug release, swelling index, drug entrapment efficiency, Fourier Transforms Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) and Differential Scanning Calorimetric (DSC) studies were also done for physicochemical characterization of the formulations.
View Article and Find Full Text PDFAim: To review published methods for detection of hepatitis B virus (HBV) infection.
Methods: A thorough search on Medline database was conducted to find original articles describing different methods or techniques of detection of HBV, which are published in English in last 10 years. Articles outlining methods of detection of mutants or drug resistance were excluded.
Chlamydia trachomatis is recognized as one of the most common sexually transmitted pathogen in the world. 50-80% of infected females are asymptomatic. These untreated women are at risk of developing chronic sequelae leading to tubal pathology causing infertility.
View Article and Find Full Text PDFBackground: Little is known about the socio-behavioral risk factors for HIV acquisition among hard-to-reach men who have sex with men (MSM) population in India, particularly from the densely populated eastern part. Thus to measure the burden and correlates of HIV among MSM in West Bengal state of eastern India, a cross-sectional analysis of the national HIV Sentinel Surveillance (HSS) data was conducted.
Methods: In 2011, between July and September, involving all sentinel sites of the state, 1237 consenting MSM were anonymously interviewed and tested for HIV following national guidelines.
Dysregulation of the innate immune response underlies numerous pathological conditions. The TLR4 is the prototypical sensor of infection or injury that orchestrates the innate response via sequential activation of both cell surface and endocytic signaling pathways that trigger distinct downstream consequences. CD14 binds and delivers LPS to TLR4 and has been identified as a positive regulator of TLR4 signal transduction.
View Article and Find Full Text PDFCD13/Aminopeptidase N is a transmembrane metalloproteinase that is expressed in many tissues where it regulates various cellular functions. In inflammation, CD13 is expressed on myeloid cells, is up-regulated on endothelial cells at sites of inflammation and mediates monocyte/endothelial adhesion by homotypic interactions. In animal models the lack of CD13 alters the profiles of infiltrating inflammatory cells at sites of ischaemic injury.
View Article and Find Full Text PDFMesenchymal stem cells (MSCs) are multipotent, tissue-resident cells that can facilitate tissue regeneration and thus, show great promise as potential therapeutic agents. Functional MSCs have been isolated and characterized from a wide array of adult tissues and are universally identified by the shared expression of a core panel of MSCs markers. One of these markers is the multifunctional cell surface peptidase CD13 that has been shown to be expressed on human and murine MSCs from many tissues.
View Article and Find Full Text PDFCD13 is a multifunctional cell surface molecule that regulates inflammatory and angiogenic mechanisms in vitro, but its contribution to these processes in vivo or potential roles in stem cell biology remains unexplored. We investigated the impact of loss of CD13 on a model of ischemic skeletal muscle injury that involves angiogenesis, inflammation, and stem cell mobilization. Consistent with its role as an inflammatory adhesion molecule, lack of CD13 altered myeloid trafficking in the injured muscle, resulting in cytokine profiles skewed toward a prohealing environment.
View Article and Find Full Text PDFCD13 is a large cell surface peptidase expressed on the monocytes and activated endothelial cells that is important for homing to and resolving the damaged tissue at sites of injury. We showed previously that cross-linking of human monocytic CD13 with activating Abs induces strong adhesion to endothelial cells in a tyrosine kinase- and microtubule-dependent manner. In the current study, we examined the molecular mechanisms underlying these observations in vitro and in vivo.
View Article and Find Full Text PDFAims: To determine the role of CD13 as an adhesion molecule in trafficking of inflammatory cells to the site of injury in vivo and its function in wound healing following myocardial infarction induced by permanent coronary artery occlusion.
Methods And Results: Seven days post-permanent ligation, hearts from CD13 knockout (CD13(KO)) mice showed significant reductions in cardiac function, suggesting impaired healing in the absence of CD13. Mechanistically, CD13(KO) infarcts showed an increase in small, endothelial-lined luminal structures, but no increase in perfusion, arguing against an angiogenic defect in the absence of CD13.
Antigen cross presentation is important for effective immune responses to tumors and viral infections. Dendritic cells are professional antigen presenting cells and are unique in their ability to cross-present exogenous antigens on MHC class I molecules and activate antigen specific cytotoxic T cells. This protocol describes antigen cross presentation by dendritic cells (DCs) (bone marrow derived DCs and splenic DCs) in an and in an assay system using soluble ovalbumin protein.
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