scholarly journals Macrophage deactivation by interleukin 10.

1991 ◽  
Vol 174 (6) ◽  
pp. 1549-1555 ◽  
Author(s):  
C Bogdan ◽  
Y Vodovotz ◽  
C Nathan
Keyword(s):  
Transforming Growth Factor Beta ◽  
Neutralizing Antibodies ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Peritoneal Macrophages ◽  
Microbial Pathogens ◽  
Tnf Alpha ◽  
Lymphocyte Function ◽  
Oxygen Intermediates ◽  
Necrosis Factor Alpha

Recombinant mouse interleukin 10 (IL-10) was exceedingly potent at suppressing the ability of mouse peritoneal macrophages (m phi) to release tumor necrosis factor alpha (TNF-alpha). The IC50 of IL-10 for the suppression of TNF-alpha release induced by 0.5 microgram/ml lipopolysaccharide was 0.04 +/- 0.03 U/ml, with as little as 1 U/ml suppressing TNF-alpha production by a factor of 21.4 +/- 2.5. At 10 U/ml, IL-10 markedly suppressed m phi release of reactive oxygen intermediates (ROI) (IC50 3.7 +/- 1.8 U/ml), but only weakly inhibited m phi release of reactive nitrogen intermediates (RNI). Since TNF-alpha is a T cell growth and differentiation factor, whereas ROI and RNI are known to inhibit lymphocyte function, it is possible that m phi exposed to low concentrations of IL-10 suppress lymphocytes. m phi deactivated by higher concentrations of IL-10 might be permissive for the growth of microbial pathogens and tumor cells, as TNF-alpha, ROI, and RNI are major antimicrobial and tumoricidal products of m phi. IL-10's effects on m phi overlap with but are distinct from the effects of the two previously described cytokines that suppress the function of mouse m phi, transforming growth factor beta and macrophage deactivation factor. Based on results with neutralizing antibodies, all three m phi suppressor factors appear to act independently.

scholarly journals Interleukin-10 inhibits interleukin-8 production in human neutrophils

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2678-2683 ◽  
Author(s):  
P Wang ◽  
P Wu ◽  
JC Anthes ◽  
MI Siegel ◽  
RW Egan ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Interleukin 8 ◽  
Tnf Alpha ◽  
Human Neutrophils ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Cytokine Synthesis

Abstract In highly purified human polymorphonuclear leukocyte (PMN) preparations containing less than 0.1% contaminating monocytes, significant amounts of interleukin-8 (IL-8) and small amounts of IL-1 alpha, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were produced by lipopolysaccharide (LPS) stimulation. Contrary to published reports, IL- 6 production could not be detected. IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-8, and TNF-alpha in LPS-stimulated PMNs, as it did in human blood mononuclear cell (MNC) preparations enriched in monocytes. Subsequent investigation of cytokine synthesis inhibitory effect of IL-10 on PMNs was focused on IL-8. IL-10 inhibited IL-8 synthesis in a dose-dependent manner and, in this regard, it was more potent than IL-4 and transforming growth factor-beta 1 (TGF-B1). In both MNCs and PMNs, degradation of LPS-induced IL-8 mRNA was enhanced by IL-10. Furthermore, as determined by nuclear run-on assays, IL-10 inhibited LPS-induced transcription of IL-8 gene in MNCs. However, in PMNs, run-on assays could not reliably detect IL-8 gene transcription. These results provide the first evidence that the human peripheral neutrophil is a target for inhibition of cytokine synthesis by IL-10, and that IL-10 acts by affecting both gene transcription and mRNA stability.

scholarly journals Interleukin-10 inhibits interleukin-8 production in human neutrophils

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2678-2683 ◽  
Author(s):  
P Wang ◽  
P Wu ◽  
JC Anthes ◽  
MI Siegel ◽  
RW Egan ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Interleukin 8 ◽  
Tnf Alpha ◽  
Human Neutrophils ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Cytokine Synthesis

In highly purified human polymorphonuclear leukocyte (PMN) preparations containing less than 0.1% contaminating monocytes, significant amounts of interleukin-8 (IL-8) and small amounts of IL-1 alpha, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were produced by lipopolysaccharide (LPS) stimulation. Contrary to published reports, IL- 6 production could not be detected. IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-8, and TNF-alpha in LPS-stimulated PMNs, as it did in human blood mononuclear cell (MNC) preparations enriched in monocytes. Subsequent investigation of cytokine synthesis inhibitory effect of IL-10 on PMNs was focused on IL-8. IL-10 inhibited IL-8 synthesis in a dose-dependent manner and, in this regard, it was more potent than IL-4 and transforming growth factor-beta 1 (TGF-B1). In both MNCs and PMNs, degradation of LPS-induced IL-8 mRNA was enhanced by IL-10. Furthermore, as determined by nuclear run-on assays, IL-10 inhibited LPS-induced transcription of IL-8 gene in MNCs. However, in PMNs, run-on assays could not reliably detect IL-8 gene transcription. These results provide the first evidence that the human peripheral neutrophil is a target for inhibition of cytokine synthesis by IL-10, and that IL-10 acts by affecting both gene transcription and mRNA stability.

scholarly journals Local and systemic influence of toxic levels of airborne ozone on the inflammatory response in rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Małgorzata Chmielewska-Krzesińska ◽  
Krzysztof Wąsowicz
Keyword(s):  
Inflammatory Response ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Interleukin 10 ◽  
Necrosis Factor Alpha ◽  
Genes Expression ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Abstract Introduction Ozone is not harmful itself; however, it directly oxidises biomolecules and produces radical-dependent cytotoxicity. Exposure to ozone is by inhalation and therefore the lungs develop the main anti-inflammatory response, while ozone has an indirect impact on the other organs. This study investigated the local and systemic effects of the ozone-associated inflammatory response. Material and Methods Three groups each of 5 Wistar Han rats aged 6 months were exposed for 2h to airborne ozone at 0.5 ppm and a fourth identical group were unexposed controls. Sacrifice was at 3h after exposure for control rats and one experimental group and at 24 h and 48 h for the others. Lung and liver samples were evaluated for changes in expression of transforming growth factor beta 1, anti-inflammatory interleukin 10, pro-inflammatory tumour necrosis factor alpha and interleukin 1 beta and two nuclear factor kappa-light-chain-enhancer of B cells subunit genes. Total RNA was isolated from the samples in spin columns and cDNA was synthesised in an RT-PCR. Expression levels were compared to those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and analysed statistically. Results All variables changed non-linearly over time comparing experimental groups to the control. Conspicuous expression changes in the subunit genes and cytokines were observed in both evaluated organs. Conclusion Locally and systemically, inflammation responses to ozone inhalation include regulation of certain genes’ expression. The mechanisms are unalike in lungs and liver but ozone exerts a similar effect in both organs. A broader range of variables influential on ozone response should be studied in the future.

scholarly journals Ability of flt3 ligand to stimulate the in vitro growth of primitive murine hematopoietic progenitors is potently and directly inhibited by transforming growth factor-beta and tumor necrosis factor-alpha

Blood ◽  
1996 ◽  
Vol 87 (12) ◽  
pp. 5016-5026 ◽  
Author(s):  
SE Jacobsen ◽  
OP Veiby ◽  
J Myklebust ◽  
C Okkenhaug ◽  
SD Lyman
Keyword(s):  
Cell Growth ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tnf Alpha ◽  
Tgf Beta ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Growth Factor Beta ◽  
Necrosis Factor

The recently cloned flt3 ligand (FL) stimulates the growth of primitive hematopoietic progenitor cells through synergistic interactions with multiple other cytokines. The present study is the first demonstrating cytokines capable of inhibiting FL-stimulated hematopoietic cell growth. Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (TGF-beta l) potently inhibited the clonal growth of murine Lin-Sca-l+ bone marrow progenitors stimulated by FL alone or in combination with granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), interleukin (IL)-3, IL-6, IL-11, or IL-12. TGF-beta 1 inhibited more than 96% of the myeloid colony formation in response to these cytokine combinations, whereas TNF-alpha reduced the number of colonies by 58% to 96% depending on the cytokine by which FL was combined. In addition, both TNF-alpha and TGF-beta 1 inhibited more than 90% of B220+ cell production from B220- bone marrow cells stimulated by FL + IL-7. The effects of TNF-alpha and TGF-beta 1 appeared to be due to a direct effect and on the early progenitors because the inhibition was observed at the single cell level, and because delayed addition of the two inhibitors for only 48 hours dramatically reduced their inhibitory effects. A neutralizing anti-TGF- beta antibody showed the presence of endogenous TGF-beta in the cultures and potently enhanced the ability of FL to stimulate progenitor cell growth in the absence of other cytokines. Agonistic antibodies specifically activating the p75 TNF receptors were more efficient than wild type murine TNF-alpha in signaling growth inhibition of Lin-Sca-l+ progenitor cells, whereas the p55 agonist had less effect than murine TNF-alpha. Finally, TGF-beta increased the number of FL + IL-11-stimulated Lin-Sca-1+ cells in the G1 phase of the cell cycle with 76%, whereas TNF-alpha only had a marginal effect on cell cycle distribution. Thus, TGF-beta, TNF-alpha, and p75 TNF receptor agonists are potent direct inhibitors of FL-stimulated progenitor cell growth in vitro.

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.

scholarly journals Phenotypic Switching in Cryptococcus neoformans Contributes to Virulence by Changing the Immunological Host Response

2008 ◽  
Vol 76 (9) ◽  
pp. 4322-4331 ◽  
Author(s):  
Abraham Guerrero ◽  
Bettina C. Fries
Keyword(s):  
Inflammatory Response ◽  
Cryptococcus Neoformans ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Interleukin 10 ◽  
Host Responses ◽  
Phenotypic Switching ◽  
Wild Type ◽  
Necrosis Factor Alpha

ABSTRACT Cryptococcus neoformans is an encapsulated opportunistic organism that can undergo phenotypic switching. In this process, the parent smooth colony (SM) switches to a more virulent mucoid colony (MC) variant. The host responses mounted against the SM and MC variants differ, and lower tissue interleukin 10 (IL-10) levels are consistently observed in lungs of MC-infected C57BL/6 and BALB/c mice. This suggested different roles of this cytokine in SM and MC infections. The objective of this study was to compare survival rates and characterize the host responses of SM- and MC-infected IL-10-depleted (IL-10−/−) mice, which exhibit a Th1-polarized immune response and are considered resistant hosts. As expected, SM-infected IL-10−/− mice survived longer than wild-type mice, whereas MC-infected IL-10−/− mice did not exhibit a survival benefit. Consistent with this observation, we demonstrated marked differences in the inflammatory responses of SM- and MC-infected IL-10−/− and wild-type mice. This included a more Th1-polarized inflammatory response with enhanced recruitment of macrophages and natural killer and CD8 cells in MC- than in SM-infected IL-10−/− and wild-type mice. In contrast, both SM-infected IL-10−/− and wild-type mice exhibited higher recruitment of CD4 cells, consistent with enhanced survival and differences in recruitment and Th1/Th2 polarization. Lung tissue levels of IL-21, IL-6, IL-4, transforming growth factor beta, IL-12, and gamma interferon were higher in MC-infected IL-10−/− and wild-type mice than in SM-infected mice, whereas tumor necrosis factor alpha levels were higher in SM-infected IL-10−/− mice. In conclusion, the MC variant elicits an excessive inflammatory response in a Th1-polarized host environment, and therefore, the outcome is negatively affected by the absence of IL-10.

scholarly journals Human interleukin-4 inhibits proliferation of megakaryocyte progenitor cells in culture

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 624-630 ◽  
Author(s):  
Y Sonoda ◽  
Y Kuzuyama ◽  
S Tanaka ◽  
S Yokota ◽  
T Maekawa ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Colony Formation ◽  
Neutralizing Antibodies ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Interleukin 4 ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Necrosis Factor Alpha

Abstract We studied the effects of recombinant human interleukin-4 (rhIL-4) on megakaryocyte colony formation from enriched hematopoietic progenitors. IL-4 strongly inhibited pure and mixed megakaryocyte colony formation in a dose-dependent manner. Formation of erythroid bursts, eosinophil colonies, and erythrocyte-containing mixed colonies was not affected by the addition of IL-4 as reported previously (Sonoda Y, et al; Blood 75:1615, 1990). Delayed addition experiments suggested that IL-4 acts on an early stage of proliferation of megakaryocyte progenitors. Neutralizing antibodies (antisera) prepared against transforming growth factor beta, tumor necrosis factor alpha, interferon alpha (IFN alpha), and IFN gamma did not affect the inhibitory effects of IL-4 on pure and mixed megakaryocyte colony formation. In addition, the inhibitory effects of IL-4 was also seen in serum-free cultures and in cultures containing highly enriched CD34+, HLA-DR+ cells as a target population. These results indicate that IL-4 may function as one of the negative regulators in human megakaryocytopoiesis in vitro.

Kinetics of cytokine expression during healing of acute colitis in mice

1996 ◽  
Vol 271 (1) ◽  
pp. G130-G136 ◽  
Author(s):  
L. A. Dieleman ◽  
C. O. Elson ◽  
G. S. Tennyson ◽  
K. W. Beagley
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Rna Extraction ◽  
Cytokine Expression ◽  
Tnf Alpha ◽  
Colonic Injury ◽  
Necrosis Factor Alpha ◽  
Inflammatory Protein ◽  
Kinetics Of

The mechanisms of wound healing in the gut are poorly understood but are mediated by cytokines in other tissues. In this study we wanted to determine which cytokines were expressed after nonspecific colonic injury, the kinetics of that expression, and how cytokine expression correlated with tissue histology. At 0, 4, 8, 12, 24, 48, and 72 h after intrarectal administration of 3% acetic acid to C3H/HeJ mice, their colons were removed for histology, organ culture, and RNA extraction. Cytokine mRNA expression for various cytokines was assessed by reverse transcriptase-polymerase chain reaction with primers specific for each cytokine. Cytokine production in organ cultures was measured with bioassays. Shortly after colonic injury and during colonic regeneration, proinflammatory cytokines such as interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein (MIP), and transforming growth factor-beta (TGF-beta) were expressed. In contrast, expression of T cell-derived cytokines was not detected at any time point. Cytokines such as IL-1 beta, IL-6, IL-10, TNF-alpha, and MIP-1 are important mediators of tissue repair and restitution after nonspecific colonic injury and may subserve a similar role in human colitis.

scholarly journals Synergy between transforming growth factor-beta and tumor necrosis factor-alpha in the induction of monocytic differentiation of human leukemic cell lines

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 626-632
Author(s):  
F De Benedetti ◽  
LA Falk ◽  
LR Ellingsworth ◽  
FW Ruscetti ◽  
CR Faltynek
Keyword(s):  
Cell Line ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Receptor Expression ◽  
Tnf Alpha ◽  
U937 Cells ◽  
Tgf Beta ◽  
Monocytic Differentiation ◽  
Necrosis Factor Alpha ◽  
Hl60 Cells

We examined the effect of transforming growth factor-beta (TGF-beta) alone and in combinations with other factors on the growth and differentiation of the human promyelocytic cell line HL60 and the human monoblastic cell line U937. Treatment with TGF-beta alone did not significantly affect growth or differentiation of HL60 cells, while it significantly inhibited proliferation and induced monocytic differentiation of a small percentage of U937 cells. Combinations of TGF-beta and tumor necrosis factor-alpha (TNF-alpha) acted in synergy to inhibit cell proliferation and to induce monocytic differentiation of both HL60 and U937 cells. In contrast, no synergy was observed when HL60 cells were treated with TGF-beta in various combinations with interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), and retinoic acid. Examination of TNF-alpha receptor expression on HL60 and U937 cells showed that these cell lines expressed comparable levels of high-affinity TNF-alpha binding sites. Treatment of HL60 and U937 cells with TGF-beta did not induce significant changes in TNF-alpha receptor expression in either cell line. In contrast, HL60 cells expressed much lower levels of TGF-beta receptors than did U937 cells. Treatment of both HL60 and U937 cells with TNF-alpha induced a dose-dependent increase in expression of TGF-beta receptors, suggesting that the synergy between TNF-alpha and TGF-beta may result, at least in part, from upregulation of TGF-beta receptor expression by TNF-alpha.

scholarly journals Effect of human recombinant cytokines on the induction of macrophage procoagulant activity

Blood ◽  
1994 ◽  
Vol 83 (1) ◽  
pp. 152-160 ◽  
Author(s):  
I Schwager ◽  
TW Jungi
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Procoagulant Activity ◽  
Delayed Type Hypersensitivity ◽  
Tnf Alpha ◽  
Heat Inactivation ◽  
Factor X ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma

Abstract A panel of human recombinant cytokines was tested for induction of procoagulant activity (PCA) in human monocyte-derived macrophages. Nonadherent culture conditions were used, and PCA was determined with whole cells rather than cell lysates. It was assured by Limulus amebocyte lysate assay that tested cytokines displayed low levels of endotoxin activity within the range of biologic activity. Additional evidence to rule out an endotoxin effect was provided by heat- inactivation experiments. Interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) were strong macrophage PCA inducers. The low level of PCA induced by IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, IL-4, IL-6, IL-10, and IFN-alpha could not be distinguished from that induced by traces of endotoxin contaminating the preparations. Transforming growth factor-beta decreased constitutively expressed PCA within 24 hours of exposure. PCA induced by IFN-gamma, IL-1 beta, and TNF-alpha depended largely on tissue factor expression, as evidenced by experiments with factor X-deficient plasma and antitissue factor antibodies. In macrophages subcultured in adherence, IL-1 beta was a strong PCA inducer, whereas IFN-gamma and TNF-alpha promoted little PCA increase. This observation and different kinetics of PCA induction suggested that mechanisms of PCA induction are distinct for the three cytokines. Thus, we showed that well-characterized cytokines critically involved in the promotion of cell-mediated antimicrobial defense/delayed-type hypersensitivity and considered for clinical application promote local fibrin deposition by a direct effect on macrophages.

Sign in / Sign up

Export Citation Format

Share Document