Influence of extracellular matrix in tumor necrosis factor-induced increase in endothelial permeability

1992 ◽  
Vol 263 (6) ◽  
pp. L627-L633 ◽  
Author(s):  
C. A. Partridge ◽  
C. J. Horvath ◽  
P. J. Del Vecchio ◽  
P. G. Phillips ◽  
A. B. Malik
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Endothelial Permeability ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Necrosis Factor ◽  
Intercellular Gaps

We examined the possibility that alterations of the extracellular matrix (ECM) contribute to the tumor necrosis factor-alpha (TNF-alpha)-induced increase in endothelial monolayer permeability. Endothelial permeability to 125I-labeled albumin was determined using bovine pulmonary microvessel endothelial cell (BPMVE) monolayers grown to confluence on microporous (0.8 microns diam) gelatin- and fibronectin-coated polycarbonate filters. Treatment of BPMVE with TNF-alpha (10(2) to 10(4) U/ml for 4–24 h) produced concentration- and time-dependent increases in endothelial permeability that paralleled the changes in morphology from cobblestone to elongated cells and the formation of prominent intercellular gaps and actin stress fibers. We examined the role of ECM in these changes using filters coated with ECM made by the BPMVE. Fresh BPMVE seeded onto filters coated with ECM produced by TNF-alpha-treated BPMVE had two- to threefold higher 125I-albumin permeability values than BPMVE monolayers seeded onto filters coated with ECM from control cells (P < 0.05). BPMVE seeded onto ECM from TNF-alpha-treated BPMVE also developed intercellular gaps and centralized actin filaments characteristic of the TNF-alpha-treated BPMVE. This effect was not attributable to TNF-alpha adsorbed to ECM. Polyacrylamide gel electrophoresis of ECM extracted from BPMVE treated with TNF-alpha showed decreased fibronectin. These findings suggest that the TNF-alpha-induced increase in endothelial permeability involves the loss of fibronectin and remodeling of the ECM. The increase in endothelial permeability may be secondary to decreased endothelial cell-ECM contacts resulting in elongation of cells and formation of intercellular gaps.

Tumor necrosis factor-alpha augments pulmonary arterial transendothelial albumin flux in vitro

1990 ◽  
Vol 258 (2) ◽  
pp. L57-L67 ◽  
Author(s):  
S. E. Goldblum ◽  
W. L. Sun
Keyword(s):  
Endothelial Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Vascular Endothelial ◽  
Temperature Dependent ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Pulmonary Arterial ◽  
Necrosis Factor

Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator of pulmonary vascular endothelial injury. We studied the effect of human recombinant TNF alpha (rTNF alpha) on transfer of 14C-labeled bovine serum albumin (BSA) across cultured bovine pulmonary arterial endothelial cell monolayers. rTNF alpha induced a dose-, time-, and temperature-dependent increment in transendothelial [14C]BSA flux. Only after an incubation time of greater than or equal to 4 h did rTNF alpha significantly (P less than 0.005) increase transendothelial albumin flux. rTNF alpha exposure times as brief as 5 min induced significantly (P less than 0.005) increased albumin transfer at 6 h. Although this initial rTNF alpha-endothelial interaction was not temperature dependent, the subsequent barrier dysfunction could only be generated at 37 degrees C. The rTNF alpha-induced changes could not be ascribed to endothelial cell cytotoxicity and was not blocked by protein synthesis inhibition. The effects of rTNF alpha on endothelial permeability were reversible and not specific for albumin transfer. Therefore, rTNF alpha may influence the movement of macromolecules across the pulmonary vascular endothelial barrier.

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.

scholarly journals Thalidomide Promotes the Release of Tumor Necrosis Factor-.ALPHA. (TNF-.ALPHA.) and Lethality by Lipopolysaccharide in Mice.

1998 ◽  
Vol 21 (6) ◽  
pp. 638-640 ◽  
Author(s):  
Masaaki ISHIKAWA ◽  
Shu-ichi KANNO ◽  
Motoaki TAKAYANAGI ◽  
Yoshio TAKAYANAGI ◽  
Ken-ichi SASAKI
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Inhibition of hepatic ketogenesis by tumor necrosis factor-alpha in rats

1992 ◽  
Vol 263 (5) ◽  
pp. E897-E902 ◽  
Author(s):  
M. Beylot ◽  
H. Vidal ◽  
G. Mithieux ◽  
M. Odeon ◽  
C. Martin
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Liver Glycogen ◽  
Tnf Alpha ◽  
Moderate Increase ◽  
Carboxylase Activity ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Tumor necrosis factor-alpha (TNF-alpha) stimulates hepatic lipogenesis. Therefore, it could play a role in the control of ketogenesis. To test this hypothesis, we measured simultaneously free fatty acids (FFA; [1–13C]palmitate) and ketone body (KB; [3,4–13C2]acetoacetate) kinetics, before and after intraperitoneal injection of saline or TNF-alpha, in postabsorptive rats or rats starved for 24 h. In both groups of rats, TNF-alpha injection did not modify insulinemia and induced a moderate increase of FFA concentrations and appearance rates (P < 0.05). Despite increased FFA availability, ketogenesis was impaired after TNF-alpha injection, as shown by lower KB concentrations and appearance rates; this effect was more important in postabsorptive than in starved rats. The percentage of FFA flux used for ketogenesis was decreased by TNF-alpha in the postabsorptive group (P < 0.05) and starved (P < 0.05) rats. In both groups, maximal liver acetyl-coenzyme A carboxylase activity and estimated phosphorylation state were not modified by TNF-alpha injection, but hepatic concentrations of citrate were increased (P < 0.05). This increased citrate level could be related to a mobilization of glucose stored as glycogen since liver glycogen was decreased by TNF-alpha injection (P < 0.05). In conclusion, TNF-alpha injection in rats decreased hepatic ketogenesis. This action could be related to an increased mobilization and utilization of carbohydrate stores.

scholarly journals Constitutive production of interleukin-6 and tumor necrosis factor- alpha from spontaneously proliferating T cells in patients with human T- cell lymphotropic virus type-I/II

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 571-574 ◽  
Author(s):  
RB Lal ◽  
DL Rudolph
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Human T Cell ◽  
Factor Alpha ◽  
Culture Supernatants ◽  
Necrosis Factor

Abstract The human T-cell lymphotropic viruses (HTLV) type I and type II are capable of inducing a variety of cellular genes, including many of the cytokines that regulate cell proliferation. To determine if the spontaneous proliferation of peripheral blood mononuclear cells from patients infected with HTLV-I and HTLV-II was related to coordinate expression of cytokines, we analyzed the levels of interleukin-1 beta (IL-1 beta), IL-2, IL-3, IL-4, IL-6, tumor necrosis factor-alpha (TNF- alpha) and interferon-tau (IFN-tau) in culture supernatants derived from spontaneously proliferating cells. Significantly elevated levels of IL-6 and TNF-alpha were present in culture supernatants from HTLV- I/II-infected individuals when compared with normal controls (P less than .01). Kinetic experiments showed that both IL-6 and TNF-alpha were elevated by day 5. None of the other cytokines (IL-1 beta, IL-2, IL-3, IL-4, and IFN-tau) were detectable in any of the culture. These data suggest that release of IL-6 and TNF-alpha may regulate lymphocyte proliferation in HTLV-I/II-infected individuals.

Plasma tumor necrosis factor-alpha during long-term endotoxemia in awake sheep

1992 ◽  
Vol 73 (5) ◽  
pp. 1831-1837 ◽  
Author(s):  
P. J. Sloane ◽  
T. H. Elsasser ◽  
J. A. Spath ◽  
K. H. Albertine ◽  
M. H. Gee
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Lymph Flow ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Endotoxin Infusion ◽  
Factor Alpha ◽  
Lung Lymph ◽  
Necrosis Factor ◽  
Lung Lymph Flow

We used a continuous 12-h infusion of Escherichia coli endotoxin (10 ng.min-1.kg-1) in 10 awake sheep equipped with a lung lymph fistula and vascular catheters to determine the time course of increased plasma tumor necrosis factor-alpha (TNF-alpha) during the infusion and a 12-h postinfusion period. Lung lymph flow increased progressively during the infusion to a peak value averaging 8.6 +/- 2.0 times the baseline flow of 6.3 +/- 1.3 g/h. During the postinfusion period, lung lymph flow remained elevated at three to four times baseline. The lymph-to-plasma protein concentration ratio was unchanged from baseline over 24 h, indicating a dramatic increase in net protein flux across pulmonary microvessels. The TNF-alpha concentration peaked early in the infusion and then declined, despite the continuing presence of endotoxin. Plasma TNF-alpha concentration increased 10-fold (0.33 +/- 0.05 ng/ml at baseline to 3.89 +/- 0.78 ng/ml peak) 2 h into the endotoxin infusion. At the end of the endotoxin infusion, plasma TNF-alpha had decreased to 1.16 +/- 0.19 ng/ml. The circulating TNF-alpha concentration did not correlate with pathophysiology or outcome in these sheep.

Sign in / Sign up

Export Citation Format

Share Document