Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: CELLS ; EXPRESSION ; GENE ; GENOME ; ENDOTOXIN-SHOCK ; TNF-ALPHA ; TRISTETRAPROLIN ; DECAY ; PROTECTS MICE ; KAPPA-B-ZETA
    Abstract: For a rapid induction and efficient resolution of the inflammatory response, gene expression in cells of the immune system is tightly regulated at the transcriptional and post-transcriptional level. The control of mRNA translation has emerged as an important determinant of protein levels, yet its role in macrophage activation is not well understood. We systematically analyzed the contribution of translational regulation to the early phase of the macrophage response by polysome fractionation from mouse macrophages stimulated with lipopolysaccharide (LPS). Individual mRNAs whose translation is specifically regulated during macrophage activation were identified by microarray analysis. Stimulation with LPS for 1 h caused translational activation of many feedback inhibitors of the inflammatory response including NF-kappaB inhibitors (Nfkbid, Nfkbiz, Nr4a1, Ier3), a p38 MAPK antagonist (Dusp1) and post-transcriptional suppressors of cytokine expression (Zfp36 and Zc3h12a). Our analysis showed that their translation is repressed in resting and de-repressed in activated macrophages. Quantification of mRNA levels at a high temporal resolution by RNASeq allowed us to define groups with different expression patterns. Thereby, we were able to distinguish mRNAs whose translation is actively regulated from mRNAs whose polysomal shifts are due to changes in mRNA levels. Active up-regulation of translation was associated with a higher content in AU-rich elements (AREs). For one example, Ier3 mRNA, we show that repression in resting cells as well as de-repression after stimulation depends on the ARE. Bone-marrow derived macrophages from Ier3 knockout mice showed reduced survival upon activation, indicating that IER3 induction protects macrophages from LPS-induced cell death. Taken together, our analysis reveals that translational control during macrophage activation is important for cellular survival as well as the expression of anti-inflammatory feedback inhibitors that promote the resolution of inflammation.
    Type of Publication: Journal article published
    PubMed ID: 24945926
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: PEPTIDE ; CELLS ; BLOOD ; CELL ; CLINICAL-TRIAL ; COMBINATION ; Germany ; PHASE-I ; DISEASE ; NEW-YORK ; PROTEIN ; SAMPLE ; SAMPLES ; PATIENT ; RESPONSES ; IMPACT ; primary ; INDUCTION ; ANTIGEN ; DENDRITIC CELLS ; T cell ; T cells ; T-CELL ; T-CELLS ; MHC ; TRIAL ; ASSAY ; tumor-infiltrating lymphocytes ; MELANOMA ; METASTATIC MELANOMA ; VACCINES ; HIGH-RISK ; PEPTIDES ; CLASS-I ; MHC class I ; VACCINE ; ELISPOT ; ELISPOT-ASSAY ; IMMUNE-RESPONSE ; vaccination ; MELANOMA PATIENTS ; IMMUNOGENICITY ; PERIPHERAL-BLOOD ; ADJUVANT ; CTL ; COLONY-STIMULATING FACTOR ; GM-CSF ; GRANULOCYTE-MACROPHAGE ; phase I studies ; GAMMA-ELISPOT ASSAY ; T-cell response ; tumor vaccine
    Abstract: Immunologic adjuvants are used to augment the immunogenicity of MHC class I-restricted peptide vaccines, but this effect has rarely been systematically evaluated in a clinical trial. We have investigated, in a phase I study, whether addition of the 2 adjuvants GM-CSF and KLH can enhance the T-cell response to MHC class I peptide vaccines. Forty-three high-risk melanoma patients who were clinically free of disease received 6 vaccinations with MHC class I-restricted tyrosinase peptides alone, with either GM-CSF or KLH or with a combination of both adjuvants. The primary end point was induction of tyrosinase-specific T cells, and serial T-cell monitoring was performed in unstimulated peripheral blood samples before and after the second, fourth and sixth vaccinations by ELISPOT assay. Tyrosinase-specific IFN-gamma-producing T cells were detected as early as 2 weeks after the second vaccination in 5 of 9 patients vaccinated with tyrosinase peptides in combination with GM-CSF and KLH but not in any patient vaccinated with tyrosinase peptides without adjuvants or in combination with either adjuvant alone. After 6 vaccinations, tyrosinase-specific T cells were found in patients immunized with peptides either without adjuvants (3 of 9 patients) or in combination with the single adjuvant GM-CSF (4 of 9 patients) but not with KLH (0 of 10 patients). Our results suggest that addition of either GM-CSF or KLH as a single adjuvant has little impact on the immunogenicity of tyrosinase peptides. The combined application of GM-CSF and KLH was associated with early induction of T-cell responses. (C) 2003 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 12569574
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: CANCER ; CELLS ; SURVIVAL ; MALIGNANCIES ; INVOLVEMENT ; microenvironment ; AUTOLOGOUS TRANSPLANTATION ; BONE-DISEASE ; FDG PET/CT ; CXCR4/SDF-1
    Abstract: CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination and poor prognosis. We evaluated the novel CXCR4 probe [(68)Ga]Pentixafor for in vivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [(68)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [(68)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [(18)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34(+) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [(68)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases.
    Type of Publication: Journal article published
    PubMed ID: 25736399
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...