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.

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

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.

scholarly journals Tumor necrosis factor-alpha and FMLP receptors are functionally linked during FMLP-stimulated activation of adherent human neutrophils

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 690-696 ◽  
Author(s):  
KJ Balazovich ◽  
SJ Suchard ◽  
DG Remick ◽  
LA Boxer
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Actinomycin D ◽  
Tnf Alpha ◽  
Human Neutrophils ◽  
Necrosis Factor Alpha ◽  
Alpha Receptors ◽  
Factor Alpha ◽  
Necrosis Factor

Human peripheral blood neutrophils (PMN) plated onto fibrinogen and activated with FMLP release H2O2 and lactoferrin, a specific granule component, with parallel kinetics. Although tumor necrosis factor-alpha (TNF alpha) only primes PMN in suspension, it is a potent agonist of adherent PMN. Activation of adherent PMN by FMLP (10(-7) mol/L) stimulated detectable release of TNF alpha within 45 minutes of stimulation, with maximal release (45.5 pg/10(6) cells) detected by 90 minutes. TNF alpha release paralleled the release of both lactoferrin and H2O2. To determine if TNF alpha plays a role in H2O2 and lactoferrin release, we investigated the effect of anti-TNF alpha antibodies on FMLP-stimulated activation of adherent PMN. A neutralizing rabbit anti-TNF alpha antibody inhibited both H2O2 and lactoferrin release stimulated by FMLP, whereas rabbit lgG, anti-HLA- A,B,C, anti-CD 14, and anti-interleukin-8 antibodies were without effect. The simultaneous addition of TNF alpha (1,000 U/mL) with anti- TNF alpha antibody reversed the inhibition seen with anti-TNF alpha alone. Furthermore, treatment of PMN with either actinomycin D or cylcoheximide resulted in partial (33%) inhibition of H2O2 and lactoferrin release, suggesting that protein synthesis is required for FMLP-mediated activation of adherent PMN. The addition of TNF alpha to either cycloheximide or of actinomycin D-treated PMN overcame the inhibition, indicating that the effect was specific for TNF alpha. The addition of antibodies against either the 55-or 75-kD TNF alpha receptors (referred to as p55 and p75, respectively) resulted in partial (32%) inhibition of FMLP-mediated activation of H2O2 and lactoferrin release, whereas a combination of both antibodies reduced their release to control levels. These data indicate that both p55 and p75 are involved in FMLP activation of adherent PMN. Taken together, these findings indicate that the production of TNF alpha and ligation of TNF alpha receptors are central to FMLP activation of PMN adherent to fibrinogen.

Role of lipopolysaccharide and tumor necrosis factor-alpha in induction of hepatocyte necrosis

1995 ◽  
Vol 269 (2) ◽  
pp. G297-G304 ◽  
Author(s):  
J. H. Wang ◽  
H. P. Redmond ◽  
R. W. Watson ◽  
D. Bouchier-Hayes
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Acute Hepatic Failure ◽  
Tnf Alpha ◽  
Enzyme Release ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

The occurrence of acute hepatic failure during systemic inflammatory response syndrome (SIRS) is related to the extent of hepatocyte (HC) damage and cell death resulting from necrosis or apoptosis. We hypothesized that proinflammatory mediators such as lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) can, either directly or indirectly through neutrophil (PMN) and Kupffer cell (KC) activation, induce HC damage and cell death, and that the mechanism is cellular necrosis rather than apoptosis. The results in this study demonstrated that LPS and TNF-alpha alone and in combination are directly cytotoxic to cultured rat HC as indicated by the hepatocellular enzyme release and HC necrosis. However, LPS and TNF-alpha, in the presence of sodium arsenite (a heat shock inducer), were unable to induce HC apoptosis. Both KC and PMN activated by either LPS or TNF-alpha induced significant hepatocellular enzyme release and HC necrosis, which was dependent on the ratio of KC and PMN to HC. It is concluded that LPS and TNF-alpha may play a central role in the development of acute hepatic failure after severe trauma and sepsis by directly or indirectly inducing HC necrosis rather than apoptosis.

Tumor necrosis factor-alpha induces Cl- and K+ secretion in human distal colon driven by prostaglandin E2

1996 ◽  
Vol 271 (4) ◽  
pp. G669-G674 ◽  
Author(s):  
H. Schmitz ◽  
M. Fromm ◽  
H. Bode ◽  
P. Scholz ◽  
E. O. Riecken ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Distal Colon ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Alpha Effect ◽  
K Secretion ◽  
Factor Alpha ◽  
Necrosis Factor

Increased levels of tumor necrosis factor-alpha (TNF-alpha) have been found in, for example, inflammatory bowel disease (IBD) and human immunodeficiency virus (HIV) infection. To investigate a possible contribution of TNF-alpha to the pathogenesis of diarrhea in these diseases, ion transport of human distal colon was studied in the Ussing chamber in vitro. Serosal addition of TNF-alpha increased short-circuit current (Isc) of partially stripped tissues in a dose-dependent manner. Maximum Isc increase of 1.8 +/- 0.2 mumol.h-1.cm-2 was reached after 60 +/- 9 min at 200 ng/ml TNF-alpha. Bidirectional tracer flux measurements revealed that TNF-alpha induced an increase in 36 Cl serosal-to-mucosal flux, a decrease in 36Cl- mucosal-to-serosal flux, and a slight increase in K+ secretion indicated by an increased secretory 86Rb net flux. In the highly differentiated colonic epithelial cell line HT-29/B6, TNF-alpha had no effect on Isc, suggesting a mediation step located in the subepithelium. This supposition was supported by measurements on totally stripped human tissues, since removal of subepithelial layers by total stripping reduced the TNF-alpha effect by 40%. Experiments with tetrodotoxin (10(-6)M) indicated that the TNF-alpha effect was not mediated by the enteric nervous system. The specific 5-lipoxygenase blocker ICI-230487 (5 x 10(-8)M) also had no effect on TNF-alpha action. In contrast, inhibition of cyclooxygenase by indomethacin (10(-6)M inhibited the effect of TNF-alpha. Radioimmunoassay of prostaglandin E2 (PGE2) in the serosal bathing solution revealed an increase in PGE2 production/release after addition of TNF-alpha, which paralleled the Isc response. We conclude that TNF-alpha changed Cl- and K+ transport toward secretion in human colon. This effect was mediated by PGE2 produced by subepithelial cells. Thus TNF-alpha could be a mediator of diarrhea during intestinal inflammation, e.g., in IBD and HIV infection.

Sign in / Sign up

Export Citation Format

Share Document