Production of interleukin-1 (IL-1) and a specific IL-1 inhibitor during human monocyte-macrophage differentiation: Influence of GM-CSF

Cytokine ◽  
1989 ◽  
Vol 1 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Pascale Roux-Lombard ◽  
Christine Modoux ◽  
Jean-Michel Dayer
Keyword(s):  
Interleukin 1 ◽  
Human Monocyte ◽  
Macrophage Differentiation ◽  
Gm Csf

scholarly journals Gamma-interferon modulates human monocyte/macrophage transferrin receptor expression

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1590-1595 ◽  
Author(s):  
R Taetle ◽  
JM Honeysett
Keyword(s):  
Binding Sites ◽  
Blood Cells ◽  
Interleukin 1 ◽  
Human Monocyte ◽  
Gamma Interferon ◽  
Receptor Expression ◽  
Biologically Active ◽  
Gm Csf ◽  
Fe Content ◽  
Slot Blot Analysis

Although circulating human monocytes do not express transferrin (Tf) receptors, cultured adherent blood cells display high-affinity Tf binding sites. In the present studies, effects of various cytokines and biologically active proteins on human monocyte/macrophage Tf receptors were investigated. After culture, Tf receptor expression by adherent blood cells was time dependent and plateaued by 7 days. The addition of interleukin-1 (IL-1), alpha-interferon (alpha-IFN), granulocyte/macrophage-colony stimulating factor (GM-CSF), or human IgG to macrophages cultured for 4 days did not alter Tf receptor expression. Fe-saturated, human Tf caused a significant, dose-dependent decrease in receptor expression. At a dose of 100 U/mL, gamma- interferon (gamma-IFN) significantly increased Tf receptor expression by macrophages cultured for 4 (230% +/- 51% of control) or 7 days (150% +/- 22%). Scatchard analyses showed increased binding sites but no change in receptor affinity. Northern and slot blot analysis of cellular mRNA from macrophages cultured for 4 to 7 days and exposed to gamma-IFN showed a two- to fivefold increase in Tf receptor mRNA, but less than or equal to 30% increase in beta-actin mRNA. Ferritin content of gamma-IFN-treated macrophages was 47% to 63% of control cells. Net uptake of 59Fe from Tf by gamma-IFN-treated cells was 10% to 17% of control, but uptake of radiolabeled Tf was comparable. When macrophages were labeled with 59Fe and then exposed to gamma-IFN, cell-associated Fe was reduced by 43%, indicating that gamma-IFN caused macrophage Fe release. gamma-IFN specifically modulates Tf receptor display by inducing Fe release and reducing cellular Fe content. Regulation of Tf receptor expression in macrophages is controlled by cellular Fe content and is thus similar to regulatory mechanisms in dividing cells.

scholarly journals Gamma-interferon modulates human monocyte/macrophage transferrin receptor expression

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1590-1595 ◽  
Author(s):  
R Taetle ◽  
JM Honeysett
Keyword(s):  
Binding Sites ◽  
Blood Cells ◽  
Interleukin 1 ◽  
Human Monocyte ◽  
Gamma Interferon ◽  
Receptor Expression ◽  
Biologically Active ◽  
Gm Csf ◽  
Fe Content ◽  
Slot Blot Analysis

Abstract Although circulating human monocytes do not express transferrin (Tf) receptors, cultured adherent blood cells display high-affinity Tf binding sites. In the present studies, effects of various cytokines and biologically active proteins on human monocyte/macrophage Tf receptors were investigated. After culture, Tf receptor expression by adherent blood cells was time dependent and plateaued by 7 days. The addition of interleukin-1 (IL-1), alpha-interferon (alpha-IFN), granulocyte/macrophage-colony stimulating factor (GM-CSF), or human IgG to macrophages cultured for 4 days did not alter Tf receptor expression. Fe-saturated, human Tf caused a significant, dose-dependent decrease in receptor expression. At a dose of 100 U/mL, gamma- interferon (gamma-IFN) significantly increased Tf receptor expression by macrophages cultured for 4 (230% +/- 51% of control) or 7 days (150% +/- 22%). Scatchard analyses showed increased binding sites but no change in receptor affinity. Northern and slot blot analysis of cellular mRNA from macrophages cultured for 4 to 7 days and exposed to gamma-IFN showed a two- to fivefold increase in Tf receptor mRNA, but less than or equal to 30% increase in beta-actin mRNA. Ferritin content of gamma-IFN-treated macrophages was 47% to 63% of control cells. Net uptake of 59Fe from Tf by gamma-IFN-treated cells was 10% to 17% of control, but uptake of radiolabeled Tf was comparable. When macrophages were labeled with 59Fe and then exposed to gamma-IFN, cell-associated Fe was reduced by 43%, indicating that gamma-IFN caused macrophage Fe release. gamma-IFN specifically modulates Tf receptor display by inducing Fe release and reducing cellular Fe content. Regulation of Tf receptor expression in macrophages is controlled by cellular Fe content and is thus similar to regulatory mechanisms in dividing cells.

scholarly journals Differential interleukin-1 elaboration by density-defined human monocyte subpopulations

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 298-301
Author(s):  
JA Elias ◽  
P Chien ◽  
KM Gustilo ◽  
AD Schreiber
Keyword(s):  
Human Blood ◽  
Interleukin 1 ◽  
Human Monocyte ◽  
Mononuclear Phagocytes ◽  
Blood Monocyte ◽  
Thymocyte Proliferation ◽  
Percoll Gradients ◽  
Human Blood Monocyte ◽  
Monocytes And Macrophages ◽  
Monocyte Subpopulations

Interleukin-1 (IL-1) is an important immunoregulatory peptide produced by monocytes and macrophages. Because mononuclear phagocytes are morphologically and functionally heterogeneous, we examined whether they differ in their ability to elaborate IL-1. We used discontinuous Percoll gradients to obtain five density-defined human blood monocyte subpopulations. Unfractionated monocytes and their subsets were compared for their ability to stimulate thymocyte proliferation. Supernatants obtained from the denser monocytes consistently contained more IL-1 activity than did supernatants from the less dense cells. This difference in IL-1 activity was the result of differences in IL-1 elaboration, not the selective production of an inhibitor of IL-1- induced thymocyte proliferation. These data demonstrate that density- defined human monocyte subpopulations differ in their capacity to elaborate IL-1.

scholarly journals Control of hemopoiesis by a bone marrow stromal cell clone: lipopolysaccharide- and interleukin-1-inducible production of colony- stimulating factors

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 682-691 ◽  
Author(s):  
D Rennick ◽  
G Yang ◽  
L Gemmell ◽  
F Lee
Keyword(s):  
Bone Marrow ◽  
Stromal Cell ◽  
Cell Clone ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Adherent Cell ◽  
Mouse Bone Marrow ◽  
Activated T Cells ◽  
Gm Csf ◽  
Cell Layers

A stromal cell line, GY30, was cloned from mouse bone marrow adherent cell layers. In culture, GY30 cells sustain the production of granulocyte-macrophage progenitor cells (GM-CFU) but fail to support the survival of pluripotential stem cells (CFU-S). GY30 cells secrete two growth factor activities distinct from interleukin-3 (IL-3), IL-2, and macrophage colony-stimulating factor (M-CSF) but functionally similar to GM-CSF and G-CSF. The production of both CSFs is increased 70- to 200-fold by treating GY30 cells with lipopolysaccharide or IL-1. RNA blot analysis reveals the presence of GM-CSF and G-CSF transcripts and demonstrates that IL-1 regulates the production of both factors at the mRNA level. Further, these studies show that the GM-CSF secreted by GY30 cells is structurally similar to the GM-CSF produced by activated T cells.

scholarly journals Interleukin-6 (IL-6) is an intermediate in IL-1-induced proliferation of leukemic human megakaryoblasts

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1972-1979 ◽  
Author(s):  
MA Brach ◽  
B Lowenberg ◽  
L Mantovani ◽  
U Schwulera ◽  
R Mertelsmann ◽  
...  
Keyword(s):  
Thymidine Incorporation ◽  
Interleukin 1 ◽  
Leukemic Cells ◽  
Megakaryoblastic Leukemia ◽  
Gm Csf ◽  
Endogenous Production ◽  
Neutralizing Monoclonal Antibody ◽  
In Vitro Effects ◽  
Stimulating Factor

Abstract We have examined the in vitro effects of recombinant human (rh) interleukin-1 (IL-1) on the growth of purified megakaryoblasts obtained from patients with acute megakaryoblastic leukemia. We demonstrate that both IL-1 alpha and IL-1 beta treatment of these cells led to stimulation of DNA synthesis (as shown by increase of 3H-thymidine incorporation up to 35-fold) and also resulted in colony formation of leukemic megakaryoblasts. However, the stimulatory effect of IL-1 was dependent on endogenous production of IL-6, because addition of neutralizing monoclonal antibody (MoAb) to IL-6 abrogated the stimulatory activity of IL-1. In contrast, neutralizing MoAbs to granulocyte (G)-colony stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF failed to counteract the growth- enhancing effects of IL-1. Leukemic megakaryoblasts accumulated IL-6 mRNA and released IL-6 protein into their culture supernatant when exposed to rh IL-1 but failed to disclose transcripts for G-, GM-, and M-CSF under these conditions. Analysis of IL-6 receptor (IL-6R) transcript levels demonstrated that megakaryoblasts constitutively expressed IL-6R mRNA and that these transcripts are down-regulated to undetectable levels upon exposure to IL-1 and IL-6. Increase of 3H- thymidine incorporation by megakaryoblasts could be duplicated by exogenous IL-6 that could be blocked by neutralizing MoAb to IL-6. In conclusion, our results suggest that leukemic megakaryoblasts could produce and secrete IL-6, and express IL-6R, and that the growth- enhancing effect of IL-1 on these cells is indirect, via production of IL-6 by leukemic cells.

Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line

10.3791/62652 ◽  
2021 ◽  
Author(s):  
Katharina M. Scheurlen ◽  
Dylan L. Snook ◽  
Sarah A. Gardner ◽  
Maurice R. Eichenberger ◽  
Susan Galandiuk
Keyword(s):  
Cell Line ◽  
Leukemia Cell ◽  
Human Monocyte ◽  
Leukemia Cell Line ◽  
Macrophage Differentiation

scholarly journals Interleukin-1, tumor necrosis factor, and the production of colony- stimulating factors by cultured mesenchymal cells

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1316-1323 ◽  
Author(s):  
CA Sieff ◽  
CM Niemeyer ◽  
SJ Mentzer ◽  
DV Faller
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Messenger Rna ◽  
Tumor Necrosis ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Mesenchymal Cells ◽  
Colony Stimulating Factors ◽  
Gm Csf ◽  
Necrosis Factor

Abstract Although the genes for four hematopoietic colony-stimulating factors (CSFs) have been cloned, neither the mechanism of the regulation of their production nor their cellular origins have been established with certainty. Monocytes are known to produce colony-stimulating and burst- promoting activities, as well as several monokines such as interleukin- 1 (IL-1) and tumor necrosis factor (TNF). These monokines indirectly stimulate other mesenchymal cells to produce certain colony-stimulating factors such as granulocyte-macrophage CSF (GM-CSF). To determine whether monocytes produce other CSFs and if so, to compare the mechanism of regulation of production with that of endothelial cells and fibroblasts, we investigated the synthesis of CSFs by monocytes, human umbilical vein endothelial cells, and fibroblasts. We used total cellular RNA blot analysis to determine interleukin-3 (IL-3), GM-CSF, granulocyte CSF (G-CSF), and monocyte CSF (M-CSF) messenger RNA (mRNA) content and immunoprecipitation or bioassay to confirm the presence of the specific secreted proteins. The results indicate that M-CSF mRNA and protein are produced constitutively by all three cell types and their level of expression does not increase after induction. In contrast, GM-CSF and G-CSF mRNAs are barely detectable in uninduced monocytes and show an increase in expression after lipopolysaccharide treatment. Retrovirus-immortalized endothelial cells, unlike primary endothelial cells or both primary and immortalized fibroblasts, produce IL-1 constitutively; this correlates with their constitutive production of GM-CSF and G-CSF. IL-3 mRNA was not detectable in any of these cells either before or after induction. The results indicate that these mesenchymal cells can produce three CSFs: GM-CSF, G-CSF, and M-CSF; furthermore, the data suggest that the mechanism of regulation of M-CSF production is different from that of GM-CSF and G-CSF, and that the latter two inducible CSFs are regulated by different factors in monocytes compared with the other mesenchymal cells.

scholarly journals Differential interleukin-1 elaboration by density-defined human monocyte subpopulations

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 298-301 ◽  
Author(s):  
JA Elias ◽  
P Chien ◽  
KM Gustilo ◽  
AD Schreiber
Keyword(s):  
Human Blood ◽  
Interleukin 1 ◽  
Human Monocyte ◽  
Mononuclear Phagocytes ◽  
Blood Monocyte ◽  
Thymocyte Proliferation ◽  
Percoll Gradients ◽  
Human Blood Monocyte ◽  
Monocytes And Macrophages ◽  
Monocyte Subpopulations

Abstract Interleukin-1 (IL-1) is an important immunoregulatory peptide produced by monocytes and macrophages. Because mononuclear phagocytes are morphologically and functionally heterogeneous, we examined whether they differ in their ability to elaborate IL-1. We used discontinuous Percoll gradients to obtain five density-defined human blood monocyte subpopulations. Unfractionated monocytes and their subsets were compared for their ability to stimulate thymocyte proliferation. Supernatants obtained from the denser monocytes consistently contained more IL-1 activity than did supernatants from the less dense cells. This difference in IL-1 activity was the result of differences in IL-1 elaboration, not the selective production of an inhibitor of IL-1- induced thymocyte proliferation. These data demonstrate that density- defined human monocyte subpopulations differ in their capacity to elaborate IL-1.

scholarly journals Cytokine production by primary bone marrow megakaryocytes

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4151-4156 ◽  
Author(s):  
S Jiang ◽  
JD Levine ◽  
Y Fu ◽  
B Deng ◽  
R London ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Gm Csf

Primary human bone marrow megakaryocytes were studied for their ability to express and release cytokines potentially relevant to their proliferation and/or differentiation. The purity of the bone marrow megakaryocytes was assessed by morphologic and immunocytochemical criteria. Unstimulated marrow megakaryocytes constitutively expressed genes for interleukin-1 beta (IL-1 beta), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha), by the polymerase chain reaction (PCR) and Northern blot analysis. At the protein level, megakaryocytes secreted significant amounts of IL-1 beta (53.6 +/- 3.6 pg/mL), IL-6 (57.6 +/- 15.6 pg/mL), and GM-CSF (24 +/- 4 pg/mL) but not TNF-alpha. Exposure of human marrow megakaryocytes to IL-1 beta increased the levels of IL-6 (87.3 +/- 2.3 pg/mL) detected in the culture supernatants. Transforming growth factor- beta was also able to stimulate IL-6, IL-1 beta, and GM-CSF secretion, but was less potent than stimulation with phorbol-12-myristate-13- acetate (PMA). The secreted cytokines acted additively to maintain and increase the number of colony-forming unit-megakaryocytes colonies (approximately 35%). These studies demonstrate the production of multiple cytokines by isolated human bone marrow megakaryocytes constitutively or stimulated in vitro. The capacity of human megakaryocytes to synthesize several cytokines known to modulate hematopoietic cells supports the concept that there may be an autocrine mechanism operative in the regulation of megakaryocytopoiesis.

Sign in / Sign up

Export Citation Format

Share Document