Search results for " Glycoproteins"
showing 10 items of 329 documents
Kininogen binding protein p33/gC1qR is localized in the vesicular fraction of endothelial cells
1996
AbstractThe endothelial protein p33/gC1qR is thought to mediate the assembly of components of the kinin-forming and complement-activating pathways on the surface of cardiovascular cells. FACS analysis of intact human umbilical vein endothelial cells using specific antibodies to p33 revealed a minor fluorescence on the cell surface whereas permeabilized cells showed a bright fluorescence indicative of an intracellular localization of p33. Immunostaining of fixed cells confirmed the predominant intracellular localization of p33. Fractionation studies demonstrated that the vesicular but not the membrane fraction of EA.hy926 cells is rich in p33. We conclude that externalization of p33 must pre…
Langerinneg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice.
2013
Psoriasis is an autoinflammatory skin disease of unknown etiology. Topical application of Aldara cream containing the Toll-like receptor (TLR)7 agonist Imiquimod (IMQ) onto patients induces flares of psoriasis. Likewise, in mice IMQ triggers pathological changes closely resembling psoriatic plaque formation. Key cytokines like IL-23 and type-I IFN (IFN-I), both being produced mainly by dendritic cells (DCs), have been implicated in psoriasis. Although plasmacytoid DCs (pDCs) are the main source of IFNα and thought to initiate disease, conventional DCs (cDCs) appear to maintain the psoriatic lesions. Any role of cDCs during lesion formation remains elusive. Here, we report that selective ac…
Interaction of TLR2 and TLR4 ligands with the N-terminal domain of Gp96 amplifies innate and adaptive immune responses.
2006
Activation of dendritic cells by ligands for Toll-like receptors (TLR) is a crucial event in the initiation of innate and adaptive immune responses. Several classes of TLR ligands have been identified that interact with distinct members of the TLR-family. TLR4 ligands include lipopolysaccharide derived from different Gram-negative bacteria and viral proteins. Recent reports have demonstrated the TLR-mediated activation of dendritic cells by heat shock proteins (HSPs). However, doubts were raised as to what extent this effect was due to lipopolysaccharide contaminations of the HSP preparations. We re-examined this phenomenon using Gp96 or its N-terminal domain, nominally endotoxin-free (0.5 …
Regulation of T cells in asthma: implications for genetic manipulation
2004
PURPOSE OF THE REVIEW Allergic asthma is a disease characterized by airway hyperresponsiveness, inflammation and remodeling. In the past few decades it has become clear that the pathogenesis and development of this disease is controlled by cytokines released by CD4 T helper type 2 lymphocytes that develop under the influence of natural killer lymphocytes. At birth, T cell priming exhibits a T helper type 2 bias and the development of the T helper phenotype is determined in the first year of life by environmental exposure to virus or bacterial substances or environmental allergens in genetically predisposed individuals. Decreased exposure to infection in early childhood has thus been linked …
IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose rece…
1998
SUMMARYOur study demonstrates that antigen-presenting liver sinusoidal endothelial cells (LSEC) induce production of interferon-gamma (IFN-γ) from cloned Th1 CD4+ T cells. We show that LSEC used the mannose receptor for antigen uptake, which further strengthened the role of LSEC as antigen-presenting cell (APC) population in the liver. The ability of LSEC to activate cloned CD4+ T cells antigen-specifically was down-regulated by exogenous prostaglandin E2 (PGE2) and by IL-10. We identify two separate mechanisms by which IL-10 down-regulated T cell activation through LSEC. IL-10 decreased the constitutive surface expression of MHC class II as well as of the accessory molecules CD80 and CD86 …
Gp91phox-containing NAD(P)H oxidase increases superoxide formation by doxorubicin and NADPH
2006
Doxorubicin is a highly effective antineoplastic drug associated with a dose-dependent cardiotoxicity that may result in irreversible cardiomyopathy and heart failure. Gene variants of the superoxide-generating enzyme NAD(P)H oxidase have recently been associated with this phenotype. We investigated the mechanism of this association using lucigenin-enhanced chemiluminescence, spectrophotometry, electrochemical sensor, and electron paramagnetic resonance spectroscopy. Superoxide production was measured in female wild-type and NAD(P)H oxidase-deficient (gp91phox knockout) mice. The magnitude of the increase in superoxide production on the addition of doxorubicin was much higher in hearts of w…
Random, asynchronous, and asymmetric transcriptional activity of enhancer-flanking major immediate-early genes ie1/3 and ie2 during murine cytomegalo…
2001
ABSTRACT The lungs are a major organ site of cytomegalovirus (CMV) pathogenesis, latency, and recurrence. Previous work on murine CMV latency has documented a high load and an even distribution of viral genomes in the lungs after the resolution of productive infection. Initiation of the productive cycle requires expression of the ie1/3 transcription unit, which is driven by the immediate-early (IE) promoter P 1/3 and generates IE1 and IE3 transcripts by differential splicing. Latency is molecularly defined by the absence of IE3 transcripts specifying the essential transactivator protein IE3. In contrast, IE1 transcripts were found to be generated focally and randomly, reflecting sporadic P …
Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies
2021
Abstract Tumor‐associated macrophages (TAMs) promote the immune suppressive microenvironment inside tumors and are, therefore, considered as a promising target for the next generation of cancer immunotherapies. To repolarize their phenotype into a tumoricidal state, the Toll‐like receptor 7/8 agonist imidazoquinoline IMDQ is site‐specifically and quantitatively coupled to single chain antibody fragments, so‐called nanobodies, targeting the macrophage mannose receptor (MMR) on TAMs. Intravenous injection of these conjugates result in a tumor‐ and cell‐specific delivery of IMDQ into MMRhigh TAMs, causing a significant decline in tumor growth. This is accompanied by a repolarization of TAMs to…
Measles virus enhances the expression of cellular immediate-early genes and DNA-binding of transcription factor AP-1 in lung epithelial A549 cells.
2002
In this work we investigated the effect of measles virus (MV) infection on the expression of immediate-early genes junB, c-jun and c-fos mRNA as well as AP-1 DNA-binding activity in the lung epithelial-like adenocarcinoma cell line A549. The transcription factor AP-1, which is a group of dimeric complexes of the Fos and Jun family proteins, is an important regulator in many cellular responses to different extracellular stimuli. Membrane cofactor protein CD46, which acts as a receptor for laboratory-adapted and vaccine strains of MV, has been reported to associate with beta1 integrin molecules, which are known to trigger signaling events and activate immediate-early genes. The expression of …
Down-regulation of human CYP3A4 by the inflammatory signal interleukin-6: molecular mechanism and transcription factors involved.
2002
The hepatic drug-metabolizing cytochrome P-450 (CYP) enzymes are down-regulated during inflammation. In vitro studies with hepatocytes have shown that the cytokines released during inflammatory responses are largely responsible for this CYP repression. However, the signaling pathways and the cytokine-activated factors involved remain to be properly identified. Our research has focused on the negative regulation of CYP3A4 (the major drug-metabolizing human CYP) by interleukin 6 (IL-6) (the principal regulator of the hepatic acute-phase response). CYP3A4 down-regulation by IL-6 requires activation of the glycoprotein receptor gp130; however, it does not proceed through the JAK/STAT pathway, a…