> link between IBD and Dioxins? didn't find one, but ...
By causing thymus atrophy and altering T cells, could TCDD indirectly
cause IBD? The thymus is an organ located in the chest cavity just
behind the sternum. It is of central im****tance in the maturation of T
cells. See related abstracts below:
From www.sciencedirect.com
Effect of TCDD on anti-CD3-induced changes in T-cell subsets and
cytokine production:
.... These data suggest that TCDD may be targeting T-helper cells
during activation resulting in activation-driven cell death
(apoptosis) rather than differentiation.
Early consequences of TCDD exposure on the activation and survival of
antigen-specific T cells.
TCDD is a potent immunotoxicant that suppresses adaptive immunity by
mechanisms that are not well defined ... the results are consistent
with our hypothesis that TCDD provides an early but inappropriate
activation signal to the antigen-specific T cells that allows, and
possibly enhances, the initial activation and proliferation of the T
cells, yet at the same time, interferes with the vital expression of
certain adhesion/costimulatory molecules that serve to enhance the
survival of the T cells. These changes result in truncated
proliferation, increased T-cell death, and suppression of the adaptive
immune response. PMID: 15310856
A constitutively active arylhydrocarbon receptor induces growth
inhibition of jurkat T cells through changes in the expression of
genes related to apoptosis and cell cycle arrest.
TCDD is known to suppress T cell-dependent immune reactions through
the activation of the arylhydrocarbon receptor (AhR). Our previous
findings suggest that TCDD inhibits the activation and subsequent
expansion of T cells following antigen stimulation in mice, leading to
a decreased level of T cell-derived cytokines involved in antibody
production ... To summarize, these results suggest that AhR activation
causes apoptosis and cell cycle arrest, especially through expression
changes in genes related to apoptosis and cell cycle arrest by the
xenobiotic response element dependent mechanism, leading to the
inhibition of T cell growth. PMID: 15069065
Immunotoxicological effects of Agent Orange exposure to the Vietnam
War Korean veterans.
Immunomodulatory effects of TCDD demonstrated using animals are thymic
atrophy, downregulation of cytotoxic T or B lymphocyte differentiation
or activation, whereas human immunotoxicities have not been
investigated well ... Overall, this study suggests that military
service in Vietnam and/or Agent Orange exposure disturbs immune-
homeostasis resulting in dysregulation of B and T cell activities.
PMID: 12916745
Effects of 2,3,7,8-TCDD and PCB 126 on human thymic epithelial cells
in vitro.
TCDD is a ubiquitously distributed xenobiotic ... In summary, TCDD and
a coplanar PCB induced terminal differentiation of human thymic
epithelial cells along with changes of integrins and other adhesion
molecules. These receptors and their interplay with the extracellular
matrix have key functions in the maturation of T-lymphocytes and it is
plausible that their alteration would be involved in TCDD-induced
immunotoxicity. PMID: 12799776
Examining the relation****p between impaired host resistance and
altered immune function in mice treated with TCDD.
Exposure to TCDD suppresses the immune response to numerous antigens,
including bacterial and viral pathogens. Although we administer a non-
lethal infection with influenza A virus, we often observe significant
mortality in TCDD-treated animals ... These results suggest that
decreased antibody production and hyperinflammation may contribute to
the death of TCDD-treated mice, and underscore the im****tance of
evaluating numerous endpoints before concluding that a chemical is or
is not immunotoxic. MID: 12748038
Influence of TCDD on the antigen-presenting activity of dendritic
cells.
We have previously shown that exposure of mice to 2,3,7, 8-
tetrachlorodibenzo-p-dioxin (TCDD) induces activation-like changes in
splenic dendritic cells (DC) in the absence of antigen challenge ...
these results suggest that the activation-like changes induced in DC
by TCDD do not suppress the ability of DC to process and present
antigen, but may enhance their ability to provide activation signals
to T cells. This, in turn, may alter the survival of the T cells, the
DC, or both, and might lead to dysregulation of the immune response.
PMID: 12604839
Persistence of decreased T-helper cell function in industrial workers
20 years after exposure to TCDD.
In experimentally exposed animals TCDD causes severe
immunosuppression. However, the overall susceptibility of humans for
the different pathological effects of TCDD has remained unclear. We
examined the long-term effects of TCDD in 11 industrial workers who
were exposed to high doses of TCDD for several years 20 years ago.
Current TCDD body burdens were still at least 10 times higher (between
43 and 874 pg/g blood far) in these exposed persons than in the
average German population ...TCDD has a long-term immunosuppressive-
effect on T-helper cell function, which is mediated more likely by a
reduced functionality of individual cells rather than by a reduction
in absolute cell numbers in the peripheral blood. PMID: 8732953
Parameters of immunological competence in subjects with high
consumption of fish contaminated with persistent organochlorine
compounds.
Consumption of fatty fish species, like salmon and herring, from the
Baltic Sea is an im****tant source of human exposure to persistent
organochlorine compounds, e.g. polychlorinated dioxins (PCDDs),
dibenzofurans (PCDFs) and biphenyls (PCBs). Many of these compounds
show immunotoxic and hepatotoxic effects in animals ... Our study
indicates that ac***ulation of persistent organochlorine compounds in
high consumers of fatty fish may adversely affect NK cell levels.
PMID: 8034358
Reduced T-helper cell function in mice exposed to TCDD.
Antibody production to the T-dependent antigen SRBC is highly
sensitive to suppression by dioxins. The present study provides
evidence for a defect in T-helper (TH) cells in TCDD-exposed mice ...
These results provide direct evidence for reduced activity of TH-cells
after exposure to TCDD. PMID: 1828636
Evidence for direct action of TCDD on thymic epithelium.
TCDD acts on selected targets within the immune system to produce a
characteristic profile of pathologic responses typified by thymic
atrophy, suppressed cellular immunity, and inhibition of antibody
production to T-lymphocyte-dependent antigens ... The results of this
study indicate that TCDD can act directly on epithelial target cells
in the thymus: one consequence of this action appears to be the
altered thymus-dependent maturation of T-lymphocyte precursors,
mediated through direct cell-cell contact between thymocytes and
thymic epithelial cells. PMID: 2996175> direct link between IBD and
Dioxins? didn't find one, but ...
By causing thymus atrophy and altering T cells, could TCDD indirectly
cause IBD? The thymus is an organ located in the chest cavity just
behind the sternum. It is of central im****tance in the maturation of T
cells. See related abstracts below:
From www.sciencedirect.com
Effect of TCDD on anti-CD3-induced changes in T-cell subsets and
cytokine production:
.... These data suggest that TCDD may be targeting T-helper cells
during activation resulting in activation-driven cell death
(apoptosis) rather than differentiation.
Early consequences of TCDD exposure on the activation and survival of
antigen-specific T cells.
TCDD is a potent immunotoxicant that suppresses adaptive immunity by
mechanisms that are not well defined ... the results are consistent
with our hypothesis that TCDD provides an early but inappropriate
activation signal to the antigen-specific T cells that allows, and
possibly enhances, the initial activation and proliferation of the T
cells, yet at the same time, interferes with the vital expression of
certain adhesion/costimulatory molecules that serve to enhance the
survival of the T cells. These changes result in truncated
proliferation, increased T-cell death, and suppression of the adaptive
immune response. PMID: 15310856
A constitutively active arylhydrocarbon receptor induces growth
inhibition of jurkat T cells through changes in the expression of
genes related to apoptosis and cell cycle arrest.
TCDD is known to suppress T cell-dependent immune reactions through
the activation of the arylhydrocarbon receptor (AhR). Our previous
findings suggest that TCDD inhibits the activation and subsequent
expansion of T cells following antigen stimulation in mice, leading to
a decreased level of T cell-derived cytokines involved in antibody
production ... To summarize, these results suggest that AhR activation
causes apoptosis and cell cycle arrest, especially through expression
changes in genes related to apoptosis and cell cycle arrest by the
xenobiotic response element dependent mechanism, leading to the
inhibition of T cell growth. PMID: 15069065
Immunotoxicological effects of Agent Orange exposure to the Vietnam
War Korean veterans.
Immunomodulatory effects of TCDD demonstrated using animals are thymic
atrophy, downregulation of cytotoxic T or B lymphocyte differentiation
or activation, whereas human immunotoxicities have not been
investigated well ... Overall, this study suggests that military
service in Vietnam and/or Agent Orange exposure disturbs immune-
homeostasis resulting in dysregulation of B and T cell activities.
PMID: 12916745
Effects of 2,3,7,8-TCDD and PCB 126 on human thymic epithelial cells
in vitro.
TCDD is a ubiquitously distributed xenobiotic ... In summary, TCDD and
a coplanar PCB induced terminal differentiation of human thymic
epithelial cells along with changes of integrins and other adhesion
molecules. These receptors and their interplay with the extracellular
matrix have key functions in the maturation of T-lymphocytes and it is
plausible that their alteration would be involved in TCDD-induced
immunotoxicity. PMID: 12799776
Examining the relation****p between impaired host resistance and
altered immune function in mice treated with TCDD.
Exposure to TCDD suppresses the immune response to numerous antigens,
including bacterial and viral pathogens. Although we administer a non-
lethal infection with influenza A virus, we often observe significant
mortality in TCDD-treated animals ... These results suggest that
decreased antibody production and hyperinflammation may contribute to
the death of TCDD-treated mice, and underscore the im****tance of
evaluating numerous endpoints before concluding that a chemical is or
is not immunotoxic. MID: 12748038
Influence of TCDD on the antigen-presenting activity of dendritic
cells.
We have previously shown that exposure of mice to 2,3,7, 8-
tetrachlorodibenzo-p-dioxin (TCDD) induces activation-like changes in
splenic dendritic cells (DC) in the absence of antigen challenge ...
these results suggest that the activation-like changes induced in DC
by TCDD do not suppress the ability of DC to process and present
antigen, but may enhance their ability to provide activation signals
to T cells. This, in turn, may alter the survival of the T cells, the
DC, or both, and might lead to dysregulation of the immune response.
PMID: 12604839
Persistence of decreased T-helper cell function in industrial workers
20 years after exposure to TCDD.
In experimentally exposed animals TCDD causes severe
immunosuppression. However, the overall susceptibility of humans for
the different pathological effects of TCDD has remained unclear. We
examined the long-term effects of TCDD in 11 industrial workers who
were exposed to high doses of TCDD for several years 20 years ago.
Current TCDD body burdens were still at least 10 times higher (between
43 and 874 pg/g blood far) in these exposed persons than in the
average German population ...TCDD has a long-term immunosuppressive-
effect on T-helper cell function, which is mediated more likely by a
reduced functionality of individual cells rather than by a reduction
in absolute cell numbers in the peripheral blood. PMID: 8732953
Parameters of immunological competence in subjects with high
consumption of fish contaminated with persistent organochlorine
compounds.
Consumption of fatty fish species, like salmon and herring, from the
Baltic Sea is an im****tant source of human exposure to persistent
organochlorine compounds, e.g. polychlorinated dioxins (PCDDs),
dibenzofurans (PCDFs) and biphenyls (PCBs). Many of these compounds
show immunotoxic and hepatotoxic effects in animals ... Our study
indicates that ac***ulation of persistent organochlorine compounds in
high consumers of fatty fish may adversely affect NK cell levels.
PMID: 8034358
Reduced T-helper cell function in mice exposed to TCDD.
Antibody production to the T-dependent antigen SRBC is highly
sensitive to suppression by dioxins. The present study provides
evidence for a defect in T-helper (TH) cells in TCDD-exposed mice ...
These results provide direct evidence for reduced activity of TH-cells
after exposure to TCDD. PMID: 1828636
Evidence for direct action of TCDD on thymic epithelium.
TCDD acts on selected targets within the immune system to produce a
characteristic profile of pathologic responses typified by thymic
atrophy, suppressed cellular immunity, and inhibition of antibody
production to T-lymphocyte-dependent antigens ... The results of this
study indicate that TCDD can act directly on epithelial target cells
in the thymus: one consequence of this action appears to be the
altered thymus-dependent maturation of T-lymphocyte precursors,
mediated through direct cell-cell contact between thymocytes and
thymic epithelial cells. PMID: 2996175
|
