Interferon-γ Increases Expression of Chemokine Receptors CCR1, CCR3, and CCR5, But Not CXCR4 in Monocytoid U937 Cells

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4444-4450 ◽  
Author(s):  
Davide Zella ◽  
Oxana Barabitskaja ◽  
Jennifer M. Burns ◽  
Fabio Romerio ◽  
Daniel E. Dunn ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Interferon Γ ◽  
Receptor Expression ◽  
U937 Cells ◽  
Cell Surface Molecule ◽  
Intracellular Calcium Mobilization ◽  
Hiv Entry ◽  
Ifn Γ ◽  
Antigen Presenting ◽  
Relationship Of

Abstract Chemokine receptors (CR), which can mediate migration of immune cells to the site of inflammation, also function as coreceptors for human immunodeficiency virus (HIV) entry into CD4+ T lymphocytes and antigen-presenting cells. We demonstrate here that interferon-γ (IFN-γ) increases the expression of chemokine receptors CCR1, CCR3, and CCR5 in monocytoid U937 cells as detected by cell surface molecule labeling and mRNA expression, as well as by intracellular calcium mobilization and cell migration in response to specific ligands. The increased expression of these chemokine receptors also results in an enhanced HIV-1 entry into cells. Our data provide evidence for a relationship of cellular pathways that are induced by IFN-γ with those that regulate chemokine receptor expression.

Interferon-γ Increases Expression of Chemokine Receptors CCR1, CCR3, and CCR5, But Not CXCR4 in Monocytoid U937 Cells

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4444-4450 ◽  
Author(s):  
Davide Zella ◽  
Oxana Barabitskaja ◽  
Jennifer M. Burns ◽  
Fabio Romerio ◽  
Daniel E. Dunn ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Interferon Γ ◽  
Receptor Expression ◽  
U937 Cells ◽  
Cell Surface Molecule ◽  
Intracellular Calcium Mobilization ◽  
Hiv Entry ◽  
Ifn Γ ◽  
Antigen Presenting ◽  
Relationship Of

Chemokine receptors (CR), which can mediate migration of immune cells to the site of inflammation, also function as coreceptors for human immunodeficiency virus (HIV) entry into CD4+ T lymphocytes and antigen-presenting cells. We demonstrate here that interferon-γ (IFN-γ) increases the expression of chemokine receptors CCR1, CCR3, and CCR5 in monocytoid U937 cells as detected by cell surface molecule labeling and mRNA expression, as well as by intracellular calcium mobilization and cell migration in response to specific ligands. The increased expression of these chemokine receptors also results in an enhanced HIV-1 entry into cells. Our data provide evidence for a relationship of cellular pathways that are induced by IFN-γ with those that regulate chemokine receptor expression.

Interferon-γ Upregulates CCR5 Expression in Cord and Adult Blood Mononuclear Phagocytes

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1137-1144 ◽  
Author(s):  
Deepa Hariharan ◽  
Steven D. Douglas ◽  
Benhur Lee ◽  
Jian-Ping Lai ◽  
Donald E. Campbell ◽  
...  
Keyword(s):  
Cell Surface ◽  
Hiv Infection ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Interferon Γ ◽  
Mononuclear Phagocytes ◽  
Cell Surface Expression ◽  
Ccr5 Expression ◽  
Hiv Entry ◽  
Ifn Γ

Abstract The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of their expression influences infectivity by HIV. We report here that interferon-γ (IFN-γ) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5 and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN-γ showed increased chemotaxis to the CCR5 ligands macrophage inflammatory protein-1 (MIP-1) and MIP-1β, confirming the functional relevance of IFN-γ–induced CCR5 expression. However, IFN-γ suppressed HIV entry into macrophages. Interestingly, we demonstrated that IFN-γ inhibited cell surface expression of CD4, the major receptor for HIV. This finding may explain the suppressive effect of IFN-γ on HIV entry into macrophages, despite its enhancing effect on the expression of CCR5 and CCR3 by these cells. In addition, IFN-γ–induced secretion of C-C chemokines (RANTES, MIP-1, and MIP-1β) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are consistent with a novel paradigm in which cytokines regulate HIV infection and leukocyte migration by reciprocal and opposing effects on the expression of CD4 and chemokine receptors.

Interferon-γ Upregulates CCR5 Expression in Cord and Adult Blood Mononuclear Phagocytes

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1137-1144 ◽  
Author(s):  
Deepa Hariharan ◽  
Steven D. Douglas ◽  
Benhur Lee ◽  
Jian-Ping Lai ◽  
Donald E. Campbell ◽  
...  
Keyword(s):  
Cell Surface ◽  
Hiv Infection ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Interferon Γ ◽  
Mononuclear Phagocytes ◽  
Cell Surface Expression ◽  
Ccr5 Expression ◽  
Hiv Entry ◽  
Ifn Γ

The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of their expression influences infectivity by HIV. We report here that interferon-γ (IFN-γ) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5 and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN-γ showed increased chemotaxis to the CCR5 ligands macrophage inflammatory protein-1 (MIP-1) and MIP-1β, confirming the functional relevance of IFN-γ–induced CCR5 expression. However, IFN-γ suppressed HIV entry into macrophages. Interestingly, we demonstrated that IFN-γ inhibited cell surface expression of CD4, the major receptor for HIV. This finding may explain the suppressive effect of IFN-γ on HIV entry into macrophages, despite its enhancing effect on the expression of CCR5 and CCR3 by these cells. In addition, IFN-γ–induced secretion of C-C chemokines (RANTES, MIP-1, and MIP-1β) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are consistent with a novel paradigm in which cytokines regulate HIV infection and leukocyte migration by reciprocal and opposing effects on the expression of CD4 and chemokine receptors.

scholarly journals Differential Regulation of Cathepsin S and Cathepsin L in Interferon γ–treated Macrophages

2003 ◽  
Vol 197 (2) ◽  
pp. 169-179 ◽  
Author(s):  
Courtney Beers ◽  
Karen Honey ◽  
Susan Fink ◽  
Katherine Forbush ◽  
Alexander Rudensky
Keyword(s):  
Cathepsin L ◽  
Specific Inhibitor ◽  
Cell Types ◽  
Interferon Γ ◽  
Cathepsin S ◽  
Antigen Presenting Cell ◽  
Relative Contribution ◽  
Helper Cell Type ◽  
Ifn Γ ◽  
Antigen Presenting

Cathepsin S (catS) and cathepsin L (catL) mediate late stages of invariant chain (Ii) degradation in discrete antigen-presenting cell types. Macrophages (Mϕs) are unique in that they express both proteases and here we sought to determine the relative contribution of each enzyme. We observe that catL plays no significant role in Ii cleavage in interferon (IFN)-γ–stimulated Mϕs. In addition, our studies show that the level of catL activity is significantly decreased in Mϕs cultured in the presence of IFN-γ whereas catS activity increases. The decrease in catL activity upon cytokine treatment occurs despite the persistence of high levels of mature catL protein, suggesting that a specific inhibitor of the enzyme is up-regulated in IFN-γ–stimulated peritoneal Mϕs. Similar inhibition of activity is observed in dendritic cells engineered to overexpress catL. Such enzymatic inhibition in Mϕs exhibits only partial dependence upon Ii and therefore, other mechanisms of catL inhibition are regulated by IFN-γ. Thus, during a T helper cell type 1 immune response catL inhibition in Mϕs results in preferential usage of catS, such that major histocompatibility complex class II presentation by all bone marrow–derived antigen-presenting cell is regulated by catS.

scholarly journals T cell-activating properties of an anti-Thy-1 monoclonal antibody. Possible analogy to OKT3/Leu-4.

1984 ◽  
Vol 159 (3) ◽  
pp. 716-730 ◽  
Author(s):  
K C Gunter ◽  
T R Malek ◽  
E M Shevach
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Molecular Complex ◽  
Lymphocyte Activation ◽  
Receptor Expression ◽  
Cell Surface Molecule ◽  
Potent Inducer ◽  
A Cell ◽  
Relationship Of

We have identified a single rat monoclonal antibody, G7, that is a potent inducer of interleukin (IL-2) production from all functioning T cell hybridomas as well as from normal T cells. G7 is also mitogenic for normal T cells and is a very effective inducer of IL-2 receptor expression. On fluorescence-activated cell sorter analysis, G7 recognized a pan-T cell antigen. Immunoprecipitation studies demonstrated that G7 recognized a cell surface molecule of 28-32 kD that appeared to be identical to Thy-1 in coprecipitation studies. In addition, G7 precipitated a protein of 50 kD. The possible relationship of the putative molecular complex identified by G7 on murine cells to the molecular complex identified on human T cells with anti-T3 reagents is discussed. In addition, G7 should prove to be a very useful reagent for studying the early events of lymphocyte activation as well as an inducer of lymphokine-rich supernatants.

scholarly journals Role of Th22 Cells in the Pathogenesis of Autoimmune Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Qi Jiang ◽  
Guocan Yang ◽  
Fan Xiao ◽  
Jue Xie ◽  
Shengjun Wang ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Chemokine Receptors ◽  
Inflammatory Diseases ◽  
Biological Effects ◽  
Cell Subset ◽  
Interferon Γ ◽  
Th22 Cells ◽  
Tnf Α ◽  
Ifn Γ

Upon antigenic stimulation, naïve CD4+T cells differentiate into different subsets and secrete various cytokines to exert biological effects. Th22 cells, a newly identified CD4+T cell subset,are distinct from the Th1, Th2 and Th17 subsets. Th22 cells secrete certain cytokines such as IL-22, IL-13 and TNF-α, but not others, such as IL-17, IL-4, or interferon-γ (IFN-γ), and they express chemokine receptors CCR4, CCR6 and CCR10. Th22 cells were initially found to play a role in skin inflammatory diseases, but recent studies have demonstrated their involvement in the development of various autoimmune diseases. Here, we review research advances in the origin, characteristics and effector mechanisms of Th22 cells, with an emphasis on the role of Th22 cells and their main effector cytokine IL-22 in the pathogenesis of autoimmune diseases. The findings presented here may facilitate the development of new therapeutic strategies for targeting these diseases.

Interferon-γ–induced membrane PAF-receptor expression confers tumor cell susceptibility to NK perforin-dependent lysis

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2329-2336 ◽  
Author(s):  
Christian Berthou ◽  
Jean-François Bourge ◽  
Yuehe Zhang ◽  
Annie Soulié ◽  
Daniela Geromin ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Nk Cells ◽  
Tumor Cells ◽  
Membrane Damage ◽  
Interferon Γ ◽  
Receptor Expression ◽  
Induced Membrane ◽  
Paf Receptor ◽  
Choline Phosphate ◽  
Ifn Γ

Abstract Perforin is known to display a membranolytic activity on tumor cells. Nevertheless, perforin release during natural killer (NK)–cell activation is not sufficient to induce membrane target-cell damage. On the basis of the ability of perforin to interact with phospholipids containing a choline phosphate headgroup, we identify the platelet-activating factor (PAF) and its membrane receptor as crucial components in tumor cell killing activity of human resting NK cells. We demonstrate for the first time that upon activation, naive NK cells release the choline phosphate–containing lysolipid PAF, which binds to perforin and acts as an agonist on perforin-induced membrane damage. PAF is known to incorporate cell membranes using a specific receptor. Here we show that interferon-γ (IFN–γ) secreted from activated NK cells ends in PAF-receptor expression on perforin-sensitive K562 cells but not on perforin-resistant Daudi cells. In order to prove the capacity of PAF to interact simultaneously with its membrane PAF receptor and with perforin, we successfully co-purified the 3 components in the presence of bridging PAF molecules. The functional activity of this complex was further examined. The aim was to determine whether membrane PAF-receptor expression on tumor cells, driven to express this receptor, could render them sensitive to the perforin lytic pathway. The results confirmed that transfection of the PAF-receptor complementary DNA into major histocompatibility complex class I and Fas-receptor negative tumor cells restored susceptibility to naive NK cells and perforin attack. Failure of IFN-γ to induce membrane PAF receptor constitutes the first described mechanism for tumor cells to resist the perforin lytic pathway.

scholarly journals Chemotaxis of Vδ2 T cells to the joints contributes to the pathogenesis of rheumatoid arthritis

2017 ◽  
Vol 76 (12) ◽  
pp. 2075-2084 ◽  
Author(s):  
Wen-Xiu Mo ◽  
Shan-Shan Yin ◽  
Hua Chen ◽  
Chen Zhou ◽  
Jia-Xin Zhou ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
T Cells ◽  
Disease Activity ◽  
Chemokine Receptors ◽  
Interferon Γ ◽  
Receptor Expression ◽  
Migration Assay ◽  
Tnf Α

ObjectivesTo explore the role of Vδ2 T cells in the pathogenesis of rheumatoid arthritis (RA).MethodsSixty-eight patients with RA, 21 patients with osteoarthritis and 21 healthy controls were enrolled in the study. All patients with RA fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA. Peripheral Vδ2T population, chemokine receptor expression and proinflammatory cytokine secretion were quantified by flow cytometry. The infiltration of Vδ2 T cells within the synovium was examined by immunohistochemistry and flow cytometry. The effect of tumour necrosis factor (TNF)-α and interleukin (IL)-6 on Vδ2 T migration was determined by flow cytometry and transwell migration assay.ResultsPeripheral Vδ2T cells, but not Vδ1 T cells, were significantly lower in patients with RA, which was negatively correlated with disease activity gauged by Disease Activity Score in 28 joints. Vδ2 T cells from RA accumulated in the synovium and produced high levels of proinflammatory cytokines including interferon-γ and IL-17. Phenotypically, Vδ2 T cells from RA showed elevated chemotaxis potential and expressed high levels of chemokine receptors CCR5 and CXCR3, which was driven by increased serum TNF-α through nuclear factor kappa B signalling. In vivo, TNF-α neutralising therapy dramatically downregulated CCR5 and CXCR3 on Vδ2 T cells and repopulated the peripheral Vδ2 T cells in patients with RA.ConclusionsHigh levels of TNF-α promoted CCR5 and CXCR3 expression in Vδ2 T cells from RA, which potentially infiltrated into the synovium and played crucial roles in the pathogenesis of RA. Targeting Vδ2 T cells might be a potential approach for RA.

scholarly journals 3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon- γ

2001 ◽  
Vol 38 (3) ◽  
pp. 242-251 ◽  
Author(s):  
Toshiko Morita ◽  
Kuniaki Saito ◽  
Masao Takemura ◽  
Naoya Maekawa ◽  
Suwako Fujigaki ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Kynurenine Pathway ◽  
Oxidase Inhibitor ◽  
Water Soluble ◽  
U937 Cells ◽  
Manganese Ions ◽  
Apoptotic Response ◽  
Xanthine Oxidase Inhibitor ◽  
Ifn Γ ◽  
Hydroxyanthranilic Acid

3-Hydroxyanthranilic acid (3-HAA), a metabolite of L-tryptophan, accumulates in monocyte-derived cells (THP-1),but not in other celllines tested(MRC9, H4, U373MG, Wil-NS), following immune stimulation that induces indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme in the L-tryptophan-kynurenine pathway. We examined whether metabolites of the L-tryptophan-kynurenine pathway act to induce apoptosis in monocytes/macrophages. Of the L-tryptophan metabolites tested, only 3-HAA at a concentration of 200µmol/L was found to induce apoptosis in THP-1 and U937 cells. The addition of ferrous or manganese ions further enhanced apoptosis and free radical formation by 3-HAA in these two types of cells. The apoptotic response induced by 3-HAA was significantly attenuated by the addition of antioxidant, α-tocopherol or Trolox (a water-soluble analogue of vitamin E), and the xanthine oxidase inhibitor, allopurinol. In addition, the 3-HAA-induced apoptotic response was slightly attenuated by catalase, but not by superoxide dismutase (SOD), indicating that generation of hydrogen peroxide is involved in this response. Interferon-γ (IFN-γ), an inducer of IDO, potently induced apoptosis in THP-1 cells, but not in U937 cells, in the presence of ferrous or manganese ions. This different susceptibility to apoptosis inducer between THP-1 and U937 cells may depend on the capacity of the cells for 3-HAA synthesis following IDO induction by IFN-γ. Furthermore, apoptosis was suppressed by cycloheximide in THP-1 cells, suggesting that newly synthesized proteins may be essential for apoptotic events. These results suggest that 3-HAA induces apoptosis in monocytes/macrophages under inflammatory or other pathophysiological conditions.

Interferon-γ–induced membrane PAF-receptor expression confers tumor cell susceptibility to NK perforin-dependent lysis

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2329-2336 ◽  
Author(s):  
Christian Berthou ◽  
Jean-François Bourge ◽  
Yuehe Zhang ◽  
Annie Soulié ◽  
Daniela Geromin ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Nk Cells ◽  
Tumor Cells ◽  
Membrane Damage ◽  
Interferon Γ ◽  
Receptor Expression ◽  
Induced Membrane ◽  
Paf Receptor ◽  
Choline Phosphate ◽  
Ifn Γ

Perforin is known to display a membranolytic activity on tumor cells. Nevertheless, perforin release during natural killer (NK)–cell activation is not sufficient to induce membrane target-cell damage. On the basis of the ability of perforin to interact with phospholipids containing a choline phosphate headgroup, we identify the platelet-activating factor (PAF) and its membrane receptor as crucial components in tumor cell killing activity of human resting NK cells. We demonstrate for the first time that upon activation, naive NK cells release the choline phosphate–containing lysolipid PAF, which binds to perforin and acts as an agonist on perforin-induced membrane damage. PAF is known to incorporate cell membranes using a specific receptor. Here we show that interferon-γ (IFN–γ) secreted from activated NK cells ends in PAF-receptor expression on perforin-sensitive K562 cells but not on perforin-resistant Daudi cells. In order to prove the capacity of PAF to interact simultaneously with its membrane PAF receptor and with perforin, we successfully co-purified the 3 components in the presence of bridging PAF molecules. The functional activity of this complex was further examined. The aim was to determine whether membrane PAF-receptor expression on tumor cells, driven to express this receptor, could render them sensitive to the perforin lytic pathway. The results confirmed that transfection of the PAF-receptor complementary DNA into major histocompatibility complex class I and Fas-receptor negative tumor cells restored susceptibility to naive NK cells and perforin attack. Failure of IFN-γ to induce membrane PAF receptor constitutes the first described mechanism for tumor cells to resist the perforin lytic pathway.

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