> direct link between IBD and Dioxins? didn't find one, but ...
Below abstract indicate that TCDD can incease TNF:
Inhibition of acute TCDD toxicity by treatment with anti-tumor
necrosis factor antibody or dexamethasone.
TCDD acute toxicity is characterized in part by a wasting syndrome
with depletion of adipose tissue. Tumor necrosis factor (TNF) induces
a similar response during chronic infection. The similarities of these
toxic effects led to a hypothesis that TNF plays a role in TCDD acute
toxicity. To test this hypothesis pharmacologic doses of an antibody
specific for murine TNF and the potent anti-inflammatory agent
Dexamethasone (DEX) were used to inhibit TCDD toxicity in mice. TNF
antibody treatment resulted in a 54% reduction in TCDD-mediated
mortality while DEX treatment, a glucocorticoid agonist that inhibits
transcription of TNF, reduced mortality by 92%. Cyp 1A1 induction, the
most commonly measured TCDD-mediated response, was not blocked by DEX,
demonstrating separation of this biochemical effect from acute toxic
responses to TCDD. These data suggest that TCDD-mediated changes in
the TNF pathway may be an im****tant mechanism for acute TCDD toxicity.
PMID: 1440607
Signaling pathway for 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced TNF-
alpha production in differentiated THP-1 human macrophages.
TCDD, a prototypic halogenated aromatic hydrocarbon (HAH), is known as
one of the most potent toxicants. At least a part of its toxic effects
appears to be derived from its ability to induce TNF-alpha
production. These results indicate that TNF-alpha production by TCDD
in differentiated THP-1 macrophages is AhR-dependent and involves
activation of EGFR and ERK, but not c-Src, JNK, nor p38 MAPK. A
signaling pathway is proposed where TCDD induces sequential activation
of AhR, EGFR and ERK, leading to the increased expression of TNF-
alpha. PMID: 17934341
The topical application of 2,3,7,8-tetrachlorodibenzo-p-dioxin lacks
skin tumor-promoting potency but induces hepatic injury and tumor
necrosis factor-alpha expression in ICR male mice.
One of the most toxic environmental pollutants known to man is
TCDD. ... severe hepatic injuries and wasting syndrome were seen in
mice treated topically with TCDD. Meanwhile, serum TNF-alpha levels
increased during the experimental periods. Inflammatory cell
infiltration, fatty liver, and nodule formation could be observed in
damaged livers. PMID: 15207371
The stimulation of tumor necrosis factor and inhibition of glucose
trans****t and lipoprotein lipase in adipose cells by TCDD
TCDD is found throughout the environment in industrialized countries,
and most people have had some exposure. TCDD has very high lipid
solubility and is concentrated in adipose tissue. ...Thus, the
addition of TCDD to adipocyte cultures resulted in an increase in TNF
secretion and a decrease in glucose trans****t and LPL activity.
Because TCDD is concentrated in adipose tissue, these studies provide
a possible physiologic mechanism for epidemiologic studies that link
dioxin to diabetes.
The effects of TCDD on TNF production by peritoneal cells.
Recent studies in mice have demonstrated that TNF plays a critical
role in mediating the TCDD-induced enhanced inflammatory response to
intraperitoneal (i.p.) sheep red blood cells. .... TCDD exposure
increases intracellular production and secretion of TNF but does not
alter levels of membrane associated TNF. PMID: 9067482
Influence of TCDD on TNF-alpha levels in the skin of congenic haired
and hairless mice.
It has been proposed that TNF-alpha mediates TCDD-induced toxicity.
TCDD induces a chloracne-like response in the skin of hairless HRS/J
mice but not in congenic haired animals. Using an ELISA, we measured
TNF-alpha levels in the skin of TCDD-treated haired and hairless HRS/J
mice to test the hypothesis that TNF-alpha mediates the cutaneous
toxicity of TCDD. TNF-alpha levels in the skin of haired mice were at
or below minimal detectable levels and were unchanged by TCDD
exposure. In contrast, TNF-alpha levels were significantly higher in
the skin of hairless mice after TCDD exposure. The bulk of the induced
TNF-alpha was present in the dermis, although detectable amounts were
present in the epidermis. PMID: 7974484
TNF involvement in TCDD endotoxin hypersensitivity in C57BL/6J mice
congenic at the Ah locus.
An experimental model of endotoxin-induced release of tumor necrosis
factor-alpha (TNF) into the serum of C57BL/6J mice congenic at the Ah
locus was used to investigate the effects of TCDD on TNF production.
TCDD exposure of Ah-responsive mice (Ahbb) resulted in a dose-
dependent increase in the concentration of TNF in the serum of
endotoxin-exposed mice, with a significant increase observed at a dose
of 10 micrograms/kg TCDD. At a dose of 500 micrograms/kg TCDD, Ahbb
mice demonstrated a 46-fold increase in serum TNF levels compared to
control. In contrast, congenic Ah-receptor deficient mice (Ahdd) did
not show a significant increase in serum TNF levels until exposed to
150 micrograms/kg TCDD, and the maximum response was an 8-fold
increase over control. These data suggest that increased TNF
production may be responsible for endotoxin hypersensitivity in TCDD-
treated mice and that the Ah locus mediates this response. PMID:
1660630
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