Differential expression of IL-1 and TNF receptors in murine macrophages infected with virulent vs. avirulentLegionella pneumophila

2000 ◽  
Vol 46 (10) ◽  
pp. 885-891 ◽  
Author(s):  
Shannon McHugh ◽  
Yoshimasa Yamamoto ◽  
Thomas W Klein ◽  
Herman Friedman
Keyword(s):  
Differential Expression ◽  
Legionella Pneumophila ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Flow Cytometric Analysis ◽  
Receptor Expression ◽  
Cytokine Receptors ◽  
Type I ◽  
Type Ii ◽  
Receptor Mrna

Infection of macrophages from genetically susceptible A/J mice with Legionella pneumophila induces high levels of various cytokines in serum as well as in cultures of spleen or peritoneal cells from the mice. However, modulation of receptor expression for these cytokines during infection has not been studied in detail, even though these receptors on macrophages have a critical role in inflammatory responses during the infection. In the present study, the differential expression of mRNA for TNF and IL-1 receptors as well as receptor antigens during infection of macrophages with virulent vs. avirulent L. pneumophila was investigated. Mouse thioglycollate-elicited peritoneal macrophages showed by RT-PCR constitutive steady-state levels of mRNA for TNF-type I and -type II receptors as well as IL-1 type I receptor. However, IL-1 type II receptor mRNA was not expressed in thioglycollate-elicited macrophages. Infection of macrophages with virulent bacteria caused an upregulation of IL-1 type I and TNF type I receptor mRNA, but had no effect on TNF type II receptor message. Avirulent L. pneumophila infection caused much less induction of these receptor mRNAs. The amount of receptor antigen of IL-1 type I on the surface of macrophages was also increased by infection with virulent L. pneumophila determined by flow cytometric analysis. These results indicate that L. pneumophila infection not only causes induction of various cytokines, but also modulation of certain cytokine receptors, which may regulate the susceptibility to infection.Key words: Legionella pneumophila, cytokine receptors, macrophages.

Abstract 16796: β2-Adrenergic Receptor Expression on Hematopoietic Cells is Critical for Survival Following Myocardial Infarction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Laurel A Grisanti ◽  
Ashley A Repas ◽  
Erhe Gao ◽  
Anna M Gumpert ◽  
Rhonda L Carter ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Bone Marrow ◽  
Cardiac Function ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Flow Cytometric Analysis ◽  
Receptor Expression ◽  
Cellular Migration ◽  
Chimeric Mice

β-adrenergic receptors (βAR) are critical regulators of cardiac function normally and during (HF). The importance of βAR on cardiomyocyte contractility and survival is well defined however, following myocardial infarction (MI), inflammatory responses occur, which are critical for healing and scar formation. Catecholamines acting through βAR, particularly the β2AR subtype, are known to modulate immune responses, however, the influence of β2AR in regulating the inflammatory response following MI is unknown. To investigate the contribution of β2AR on immune cells following myocardial infarction (MI), wild-type (WT) mice were irradiated and then received β2ARKO or WT control BM transplants to create immune cell specific knockout (KO) animals. Following bone marrow reconstitution, mice were subjected to MI and cardiac function and survival were monitored. Cardiac function, as assessed by echocardiography, did not differ between WT and β2ARKO chimeric mice. However, mice lacking β2ARKO in their BM resulted in 100% mortality from cardiac rupture within two weeks of receiving MI in contrast to their WT counterparts that had ~20% death. Masson trichrome staining demonstrated infarct expansion in β2ARKO chimeric mice occurred more rapidly than their WT counterparts. Flow cytometric analysis showed decreased mobilization of granulocytes from bone marrow in β2ARKO mice. Additionally, β2ARKO chimeric mice reductions in infiltrating monocyte/macrophage, neutrophil and mast cell populations in the heart with no change in total cell infiltration suggesting a disruption in the ratio of infiltrating immune cells. Alterations in chemokine receptor levels, particularly CCR2, on BM resulted in decreased cellular migration. These results demonstrate the critical role of β2AR in mounting an immune response and promoting healing following MI.

scholarly journals Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis

Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 757-764 ◽  
Author(s):  
Y Shima ◽  
N Nishimoto ◽  
A Ogata ◽  
Y Fujii ◽  
K Yoshizaki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Stem Cell Factor ◽  
Flow Cytometric Analysis ◽  
Myeloma Cell ◽  
Receptor Expression ◽  
Type I ◽  
Type Ii ◽  
Fas Antigen ◽  
Myeloma Cells

To find out which cytokines are involved in the pathogenesis of multiple myeloma, we investigated cytokine receptor expression on myeloma cells using a panel of monoclonal antibodies (MoAbs). Flow cytometric analysis of five myeloma cell lines (RPMI8226, ARH77, KMM-1, U266, and Hs) and myeloma cells freshly isolated from eight patients showed that interleukin-1 receptor (IL-1R) type I and type II, IL-2R alpha and beta chains, IL-4R, IL-6R, IL-7R, IL-8R, granulocyte macrophage colony-stimulating factor receptor (GM-CSFR), c-kit (stem cell factor receptor [SCFR]), membrane bound stem cell factor (MBSCF), and tumor necrosis factor (TNF) receptors type I and type II were not always detected on the myeloma cells. However, interferon-gamma receptor, gp130, and Fas antigen were constitutively expressed, except one sample. To determine the role of Fas antigen on myeloma cells, these cells were cultured with anti-Fas MoAb. Apoptotic changes characterized by loss of cell volume, membrane blebbing, fragmentation of nuclei, and condensed chromatin were observed in three of five myeloma cell lines. When bcl-2 expression was examined, it was seen in all the cell lines regardless of the sensitivity to anti-Fas MoAb. Furthermore, anti-Fas MoAb not only induced apoptosis of freshly isolated myeloma cells but also inhibited the DNA synthesis, although such effects varied from patient to patient. The data indicate that only some myeloma cells undergo apoptosis in response to the signal mediated by the Fas antigen.

FRI-317-Progression of fatty liver disease to steatohepatitis and liver fibrosis is associated with altered Oncostatin M type I and type II receptor expression

2019 ◽  
Vol 70 (1) ◽  
pp. e536
Author(s):  
Philipp Lederer ◽  
Martin Roderfeld ◽  
Daniela Kroy ◽  
Elke Roeb ◽  
Andreas Geier ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Receptor Expression ◽  
Oncostatin M ◽  
Type I ◽  
Type Ii

Cytokines and endotoxin induce cytokine receptors in skeletal muscle

2000 ◽  
Vol 279 (1) ◽  
pp. E196-E205 ◽  
Author(s):  
Yan Zhang ◽  
Geneviève Pilon ◽  
André Marette ◽  
Vickie E. Baracos
Keyword(s):  
Skeletal Muscle ◽  
Interleukin 1 ◽  
Intraperitoneal Administration ◽  
Interferon Γ ◽  
Receptor Expression ◽  
Cytokine Receptor ◽  
Cytokine Receptors ◽  
Type I ◽  
Skeletal Muscle Function ◽  
Tnf Α

Proinflammatory cytokines are important factors in the regulation of diverse aspects of skeletal muscle function; however, the muscle cytokine receptors mediating these functions are uncharacterized. Binding kinetics (dissociation constant = 39 ± 4.7 × 10−9M, maximal binding = 3.5 ± 0.23 × 10−12mol/mg membrane protein) of muscle tumor necrosis factor (TNF) receptors were obtained. Skeletal muscle was found to express mRNAs encoding interleukin-1 type I and II receptors, interleukin-6 receptor (IL-6R), and interferon-γ receptor by RT-PCR, but these receptors were below limits of detection of ligand-binding assay (≥1 fmol binding sites/mg protein). Twenty-four hours after intraperitoneal administration of endotoxin to rats, TNF receptor type II (TNFRII) and IL-6R mRNA were increased in skeletal muscle ( P < 0.05). In cultured L6 cells, the expression of mRNA encoding TNFRII and IL-6R receptors was induced by TNF-α, and all six cytokine receptor mRNA were induced by a mixture of TNF-α, IFN-γ, and endotoxin ( P < 0.05). This suggests that the low level of cytokine receptor expression is complemented by a capacity for receptor induction, providing a clear mechanism for amplification of cytokine responses at the muscle level.

scholarly journals Type I and Type II Interleukin-1 Receptor Expression in Rat, Mouse, and Human Testes1

1997 ◽  
Vol 56 (6) ◽  
pp. 1513-1526 ◽  
Author(s):  
Edith Gomez ◽  
Gérard Morel ◽  
Annie Cavalier ◽  
Marie-Odile Liénard ◽  
France Haour ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Receptor Expression ◽  
Type I ◽  
Type Ii

scholarly journals Integrin β1Signaling Is Necessary for Transforming Growth Factor-β Activation of p38MAPK and Epithelial Plasticity

2001 ◽  
Vol 276 (50) ◽  
pp. 46707-46713 ◽  
Author(s):  
Neil A. Bhowmick ◽  
Roy Zent ◽  
Mayshan Ghiassi ◽  
Maureen McDonnell ◽  
Harold L. Moses
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Transcriptional Activation ◽  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Dominant Negative ◽  
Receptor Expression ◽  
Type I ◽  
Type Ii

Transforming growth factor-β (TGF-β) can induce epithelial to mesenchymal transdifferentiation (EMT) in mammary epithelial cells. TGF-β-meditated EMT involves the stimulation of a number of signaling pathways by the sequential binding of the type II and type I serine/threonine kinase receptors, respectively. Integrins comprise a family of heterodimeric extracellular matrix receptors that mediate cell adhesion and intracellular signaling, hence making them crucial for EMT progression. In light of substantial evidence indicating TGF-β regulation of various β1integrins and their extracellular matrix ligands, we examined the cross-talk between the TGF-β and integrin signal transduction pathways. Using an inducible system for the expression of a cytoplasmically truncated dominant negative TGF-β type II receptor, we blocked TGF-β-mediated growth inhibition, transcriptional activation, and EMT progression. Dominant negative TGF-β type II receptor expression inhibited TGF-β signaling to the SMAD and AKT pathways, but did not block TGF-β-mediated p38MAPK activation. Interestingly, blocking integrin β1function inhibited TGF-β-mediated p38MAPK activation and EMT progression. Limiting p38MAPK activity through the expression of a dominant negative-p38MAPK also blocked TGF-β-mediated EMT. In summary, TGF-β-mediated p38MAPK activation is dependent on functional integrin β1, and p38MAPK activity is required but is not sufficient to induce EMT.

Clinical Application of Matrix Metalloproteinase-8 and Matrix Metalloproteinase-9 Expression in Patients with CML.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3795-3795
Author(s):  
Liang-In Lin ◽  
Cheng-Yeh Lee ◽  
Dong-Tsamn Lin ◽  
Hwei-Wen Wen ◽  
Hwei-Fang Tien
Keyword(s):  
Differential Diagnosis ◽  
Matrix Metalloproteinase ◽  
Proteolytic Enzymes ◽  
Critical Role ◽  
Flow Cytometric Analysis ◽  
Surrogate Marker ◽  
Immunocytochemical Staining ◽  
Type I ◽  
Leukemoid Reaction ◽  
Normal Individuals

Abstract Neutrophils are the first cells to arrive at the site of infection where they play a critical role in host defense against invading microbes. To perform this process, neutrophils produce and secrete a lot of molecules to destroy the infectious agent. Among proteolytic enzymes identified in the neutrophils, matrix metalloproteinases (MMPs) have attracted considerable attention for their proposed role in the destruction of extracellular matrix under physiological and pathological conditions. The first MMP identified in neutrophils is MMP-8 or neutrophil collagenase that is stored in the specific granules and is capable of cleaving type I collagen. MMP-9, neutrophil gelatinase, are stored in the gelatinase granules and is capable of cleaving type VI collagen. Chronic myeloid leukemia (CML) is a malignant clonal disorder that originates from a transformed stem cell and involves myeloid lineage. The affected cells have both proliferative and functional impairment. Leukemoid reaction (LR) often encountered in association with severe infections or malignancy, shows extreme elevations of the leukocyte count with left shift including myeocytes, promyelocytes and blasts that would be confused with CML. The laboratory differential diagnosis of CML and LR are based on the leukocyte alkaline phosphatase (LAP) score, philadelphia chromosome analysis and bone marrow analysis. Our previous study revealed that the level of marrow MMP-9 may be a useful surrogate marker for monitoring disease status in AML and propose it as a potential prognostic factor. In this study, CML patients at diagnosis, various patients with leukemoid reaction and several normal individuals were assessed, to evaluate the potentiality of MMP-9 or/and MMP-8 to be differential diagnostic markers between CML and LR. We determined the MMP-8 and MMP-9 concentrations in peripheral blood by ELISA method, and the MMP-8 and MMP-9 contents in neutrophils by immunocytochemical staining and flow cytometry. We found that the plasma MMP-8 levels were less than 10ng/ml in all normal individuals studied, those were 10 – 100ng/ml in CML patients and those were more than 100ng/ml in LR patients. The same trend was shown in MMP-9 levels, which were less than 50ng/ml, 50 – 450ng/ml and more than 450ng/ml, respectively. Immunocytochemical staining revealed MMP-8 and MMP-9 contents in cytoplasm of neutrophils were abundant in patients with LR, compared with those in patients with CML and normal individuals; further flow cytometric analysis also showed the same trend. These results suggest that the MMP-8 and MMP-9 concentrations and individual neutrophil MMP-8 and MMP-9 contents might contribute to discriminate between CML and LR, and to be useful surrogate markers for differential diagnosis.

scholarly journals Stat-mediated Signaling Induced by Type I and Type II Interferons (IFNs) Is Differentially Controlled through Lipid Microdomain Association and Clathrin-dependent Endocytosis of IFN Receptors

2006 ◽  
Vol 17 (7) ◽  
pp. 2896-2909 ◽  
Author(s):  
Marta Marchetti ◽  
Marie-Noelle Monier ◽  
Alexandre Fradagrada ◽  
Keith Mitchell ◽  
Florence Baychelier ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Biological Activities ◽  
Critical Role ◽  
Membrane Lipid ◽  
Endocytic Pathway ◽  
Type I ◽  
Type Ii ◽  
Biological Responses ◽  
Signal Specificity ◽  
Ifn Γ

Type I (α/β) and type II (γ) interferons (IFNs) bind to distinct receptors, although they activate the same signal transducer and activator of transcription, Stat1, raising the question of how signal specificity is maintained. Here, we have characterized the sorting of IFN receptors (IFN-Rs) at the plasma membrane and the role it plays in IFN-dependent signaling and biological activities. We show that both IFN-α and IFN-γ receptors are internalized by a classical clathrin- and dynamin-dependent endocytic pathway. Although inhibition of clathrin-dependent endocytosis blocked the uptake of IFN-α and IFN-γ receptors, this inhibition only affected IFN-α–induced Stat1 and Stat2 signaling. Furthermore, the antiviral and antiproliferative activities induced by IFN-α but not IFN-γ were also affected. Finally, we show that, unlike IFN-α receptors, activated IFN-γ receptors rapidly become enriched in plasma membrane lipid microdomains. We conclude that IFN-R compartmentalization at the plasma membrane, through clathrin-dependent endocytosis and lipid-based microdomains, plays a critical role in the signaling and biological responses induced by IFNs and contributes to establishing specificity within the Jak/Stat signaling pathway.

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