Mutual antagonism between interferon-gamma and tumor necrosis factor-alpha on fibroblast-like synoviocytes: Paradoxical induction of IFN-gamma and TNF-alpha receptor expression

1993 ◽  
Vol 13 (3) ◽  
pp. 212-218 ◽  
Author(s):  
Jose M. Alvaro-Gracia ◽  
Caroline Yu ◽  
Nathan J. Zvaifler ◽  
Gary S. Firestein
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Receptor Expression ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Mutual Antagonism ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Fibroblast Like Synoviocytes

scholarly journals Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1392-1397 ◽  
Author(s):  
AA te Velde ◽  
RJ Huijbens ◽  
K Heije ◽  
JE de Vries ◽  
CG Figdor
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Time Course ◽  
Interleukin 4 ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Factor Alpha ◽  
Necrosis Factor

Monocytes activated by lipopolysaccharide (LPS) and interferon gamma (IFN gamma) rapidly secrete a number of monokines with different functional properties. Interleukin–4 (IL–4), a T-cell derived cytokine, has been shown to reduce the production of monokines with cytostatic activity for tumor cells, chemotactic activity for monocytes, and factors that stimulate thymocyte proliferation. This latter activity is mediated by a number of monokines like IL–1, tumor necrosis factor alpha (TNF alpha), and IL–6. To elucidate which cytokines produced by monocytes are controlled by IL–4, we tested the effect of IL–4 on the secretion of IL–1 alpha, IL–1 beta, TNF alpha, and IL–6 induced by LPS or IFN gamma. IL–4 was found to inhibit the secretion of IL–1 beta and TNF alpha by activated monocytes almost 100%. The secretion of IL–6 was found to be reduced 70% to 85% in the presence of IL–4, whereas there was no effect on the secretion of IL–1 alpha (IL–1 alpha is mainly cell- associated). Time-course experiments demonstrate that IL–4 reduces the secretion of monokines for a prolonged period of time (greater than 40 hours). The reduced secretion of IL–1 beta and TNF alpha was specifically induced by IL–4 because anti-IL–4 antiserum completely restored normal monokine production. These data suggest that IL–4 plays a role in the regulation of immune responses by reducing the production of functionally important monokines.

scholarly journals Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1392-1397 ◽  
Author(s):  
AA te Velde ◽  
RJ Huijbens ◽  
K Heije ◽  
JE de Vries ◽  
CG Figdor
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Time Course ◽  
Interleukin 4 ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Factor Alpha ◽  
Necrosis Factor

Abstract Monocytes activated by lipopolysaccharide (LPS) and interferon gamma (IFN gamma) rapidly secrete a number of monokines with different functional properties. Interleukin–4 (IL–4), a T-cell derived cytokine, has been shown to reduce the production of monokines with cytostatic activity for tumor cells, chemotactic activity for monocytes, and factors that stimulate thymocyte proliferation. This latter activity is mediated by a number of monokines like IL–1, tumor necrosis factor alpha (TNF alpha), and IL–6. To elucidate which cytokines produced by monocytes are controlled by IL–4, we tested the effect of IL–4 on the secretion of IL–1 alpha, IL–1 beta, TNF alpha, and IL–6 induced by LPS or IFN gamma. IL–4 was found to inhibit the secretion of IL–1 beta and TNF alpha by activated monocytes almost 100%. The secretion of IL–6 was found to be reduced 70% to 85% in the presence of IL–4, whereas there was no effect on the secretion of IL–1 alpha (IL–1 alpha is mainly cell- associated). Time-course experiments demonstrate that IL–4 reduces the secretion of monokines for a prolonged period of time (greater than 40 hours). The reduced secretion of IL–1 beta and TNF alpha was specifically induced by IL–4 because anti-IL–4 antiserum completely restored normal monokine production. These data suggest that IL–4 plays a role in the regulation of immune responses by reducing the production of functionally important monokines.

scholarly journals Regulation of cytokine production by soluble CD23: costimulation of interferon gamma secretion and triggering of tumor necrosis factor alpha release.

1994 ◽  
Vol 180 (3) ◽  
pp. 1005-1011 ◽  
Author(s):  
M Armant ◽  
H Ishihara ◽  
M Rubio ◽  
G Delespesse ◽  
M Sarfati
Keyword(s):  
Tumor Necrosis Factor ◽  
Interferon Gamma ◽  
Tumor Necrosis ◽  
Cytokine Production ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Alpha Production ◽  
Factor Alpha ◽  
Necrosis Factor

Soluble CD23 (sCD23) has multiple IgE-independent biological activities. In the present study, we examined the regulatory effect of sCD23 on cytokine production by human peripheral blood mononuclear cells (PBMC). We show that sCD23 enhances by about 80-fold the interleukin 2 (IL-2)-induced interferon gamma (IFN-gamma) production and by about 10-fold the response to IL-12. This potentiating activity is time and dose dependent and is not associated with a significant effect on DNA synthesis. The sCD23 costimulatory activity for IFN-gamma synthesis is drastically reduced in monocyte-depleted PBMC, suggesting that monocytes may be the target for sCD23. This hypothesis was supported by the following observations. First, sCD23 alone is a potent inducer of tumor necrosis factor alpha (TNF-alpha) production by PBMC and this effect disappears after monocyte depletion. The triggering of TNF-alpha release is specifically inhibited by neutralizing anti-CD23 monoclonal antibody (mAb). In addition, IL-2 and IL-12 synergize with sCD23 to induce TNF-alpha production. Second, sCD23 triggers the release of other inflammatory mediators such as IL-1 alpha, IL-1 beta, and IL-6. Finally, TNF-alpha production in response to IL-2 and sCD23 precedes IFN-gamma and IFN-gamma secretion is significantly inhibited by anti-TNF-alpha mAb, indicating that the sCD23 costimulatory signal for IFN-gamma production may be partially mediated by TNF-alpha release. It is proposed that sCD23 is a proinflammatory cytokine that, in addition, may play an important role in the control of the immune response via the enhancement of IFN-gamma production.

In Vitro Effects of 1,25-Dihydroxyvitamin D3 on Interferon-gamma and Tumor Necrosis Factor-alpha Secretion by Blood Leukocytes from Young and Adult Cattle Vaccinated with Mycobacterium bovis BCG

2003 ◽  
Vol 73 (4) ◽  
pp. 235-244 ◽  
Author(s):  
Nonnecke ◽  
Waters ◽  
Foote ◽  
Horst ◽  
Fowler ◽  
...  
Keyword(s):  
Vitamin D ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Primary Vaccination ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Factor Alpha ◽  
Necrosis Factor

Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) are critical in the development of an effective immune response. Vitamin D, essential in short-term calcium homeostasis and recently shown to modulate proliferation and function of blood mononuclear cells from adult dairy cattle, may be an effective modulator of the calf’s immune system. Effects of antigen sensitization and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on cytokine secretion by cells from calves vaccinated with Bacille Calmette-Guérin (BCG) were examined. One-week-old dairy calves (n = 6) and yearling heifers (n = 4) were vaccinated concurrently with BCG and boosted six weeks later. Ten weeks after primary vaccination, cells from vaccinated calves and adults, and nonvaccinated, age-matched calves (n = 4) were evaluated in vitro for their capacity to produce IFN-gamma and TNF-alpha. Cells were stimulated with pokeweed mitogen (PWM) or recall antigen [Mycobacterium bovis-derived purified protein derivative (PPD)] in the presence of 0, 0.1, 1.0, and 10nM of 1,25-(OH)2D3 for 20, 44, and 68 hours, respectively. IFN-gamma and TNF-alpha concentrations in culture supernatants harvested at these times were quantified by enzyme-linked immunosorbent assay (ELISA). PPD-induced IFN-gamma and TNF-alpha responses of cells from vaccinated calves and adults were greater than responses of autologous unstimulated cells. In contrast, PPD-specific responses of calf and adult cells collected immediately before primary vaccination were substantially lower and comparable to responses in resting (i.e., unstimulated) cultures. At ten weeks, the PPD-specific response of vaccinates exceeded the response of nonvaccinated calves; however, responses of vaccinated calves were more vigorous than corresponding responses of vaccinated adults. Incubation period also influenced the magnitude of both IFN-gamma and TNF-alpha responses in PPD- and PWM-stimulated cultures. Effects of 1,25-(OH)2D3 on antigen-induced secretion of IFN-gamma and TNF-alpha were marginal. Only IFN-gamma responses of vaccinated adults were affected by 1,25-(OH)2D3. Vitamin D caused a concentration-dependent decrease in IFN-gamma response and an increase in TNF-alpha response in PWM-stimulated cultures. These results indicate that animal maturity (i.e., age) and antigenic experience affect IFN-gamma and TNF-alpha secretion by bovine leukocytes and suggest that 1,25-(OH)2D3 can alter secretion of both cytokines under specific conditions of culture.

Protein myristoylation in human mononclear phagocytes: modulation by interferon-gamma and tumor necrosis factor-alpha

1991 ◽  
Vol 100 (4) ◽  
pp. 833-840
Author(s):  
G. Poli ◽  
C. Sorio ◽  
G. Berton
Keyword(s):  
Tumor Necrosis Factor ◽  
Interferon Gamma ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Factor Alpha ◽  
Protein Myristoylation ◽  
Necrosis Factor

Labelling of cells with [3H]myristic acid and analysis of labelled proteins by SDS-PAGE and fluorography, enabled the identification of a limited number of myristoylated proteins in human monocytes and monocyte-derived macrophages. In human monocytes, cultivated for one to three days, major myristoylated proteins observed were of 18 kDa, 44 kDa, 60–62 kDa, 90 kDa, and a doublet of 38–40 kDa. Differentiation of monocytes to macrophages by in vitro cultivation was accompanied by a selective decrease in the 60–62 kDa protein. Cultivation of the cells in the presence of the macrophage-activating cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), prevented the decrease in the expression of the 60–62 kDa myristoylated protein. The effect of cytokines was observed when monocytes were treated with IFN-gamma or TNF-alpha for 24 or 48 h and protein myristoylation analyzed at day four of culture. Maintenance of monocytes in culture for up to nine days in the presence of cytokines prevented the decrease in the expression of the 60–62 kDa myristoylated protein. IFN-gamma had additional effects on myristoylation of macrophage proteins. Treatment of monocytes with IFN-gamma for a few hours caused the induction of a 66 kDa protein. Induction of this myristoylated protein by IFN-gamma was time-dependent and peaked at six hours. Analysis of the subcellular distribution of the 66 kDa protein induced by IFN-gamma showed that, analogously to other myristoylated proteins, most of it was associated with cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor necrosis factor-alpha inhibits lipid and lipoprotein transport by Caco-2 cells

1995 ◽  
Vol 269 (6) ◽  
pp. G953-G960 ◽  
Author(s):  
M. Mehran ◽  
E. Seidman ◽  
R. Marchand ◽  
C. Gurbindo ◽  
E. Levy
Keyword(s):  
Lipid Metabolism ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Low Density Lipoproteins ◽  
Tnf Alpha ◽  
Low Density ◽  
Necrosis Factor Alpha ◽  
Apo B ◽  
Factor Alpha ◽  
Necrosis Factor

Cytokines, important mediators of inflammation, have been shown to cause disturbances in circulating and hepatic lipid metabolism. Although the intestine plays a major role in dietary fat transport and largely contributes to plasma lipoproteins, the effects of cytokines on intestinal lipid handling remain unknown. In the present study, the modulation of lipid, apoprotein, and lipoprotein synthesis and secretion by tumor necrosis factor-alpha (TNF-alpha) was investigated in Caco-2 cells. Highly differentiated and polarized cells (20 days in culture) were incubated for 20 h with recombinant human TNF-alpha (100-500 ng/ml). No cytotoxic effect of TNF-alpha cells was observed, as indicated by the determinations of Caco-2 cell viability and monolayer transepithelial resistance. Moreover, no differences in cell maturation (sucrase activity) or cell proliferation ([3H]thymidine incorporation and cell cycle analysis) were detected between treated and control cultures. Significant inhibition of lipid secretion by TNF-alpha was observed, with the greatest reduction at 500 ng/ml. TNF-alpha significantly decreased Caco-2 cell secretion of phospholipids (22%), triglycerides (30%), and cholesteryl ester (37%). It also significantly diminished the export of newly synthesized low-density lipoproteins (LDL; 20%) and high-density lipoproteins (HDL; 13%), with a lesser effect on very low-density lipoproteins (VLDL; 3%). The lipid composition of these lipoproteins was minimally affected. De novo synthesis of apo A-I, apo B-100, and apo B-48 was also markedly reduced by TNF-alpha. Sphingomyelinase activity was not increased and cell content of sphingomyelin was not altered, suggesting that inhibitory effects on lipid and apoprotein of TNF-alpha were not mediated by the ceramide pathway. Our results indicate that TNF-alpha may play a role in modulating intestinal lipid metabolism, thus affecting circulating lipoproteins.

NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-6 gene by tumor necrosis factor alpha and interleukin-1

1994 ◽  
Vol 14 (10) ◽  
pp. 6561-6569
Author(s):  
L Klampfer ◽  
T H Lee ◽  
W Hsu ◽  
J Vilcek ◽  
S Chen-Kiang
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Human Fibroblasts ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Normal Human ◽  
Factor Alpha ◽  
Necrosis Factor

Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) activate transcription of the TSG-6 gene in normal human fibroblasts through a promoter region (-165 to -58) that encompasses an AP-1 and a NF-IL6 site. We show by deletion analysis and substitution mutagenesis that both sites are necessary for activation by TNF-alpha. Activation by IL-1 requires the NF-IL6 site and is enhanced by the AP-1 site. These results suggest that the NF-IL6 and AP-1 family transcription factors functionally cooperate to mediate TNF-alpha and IL-1 signals. Consistent with this possibility, IL-1 and TNF-alpha markedly increase the binding of Fos and Jun to the AP-1 site, and NF-IL6 activates the native TSG-6 promoter. Activation by NF-IL6 requires an intact NF-IL6 site and is modulated by the ratio of activator to inhibitor NF-IL6 isoforms that are translated from different in-frame AUGs. However, the inhibitor isoform can also bind to the AP-1 site and repress AP-1 site-mediated transcription. The finding that the inhibitor isoform antagonizes activation of the native TSG-6 promoter by IL-1 and TNF-alpha suggests that NF-IL6 has a physiologic role in these cytokine responses. Thus, the functionally distinct NF-IL6 isoforms cooperate with Fos and Jun to positively and negatively regulate the native TSG-6 promoter by TNF-alpha and IL-1.

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