Ironjustic
Wed, May-21-08, 17:16
Inflammatory Response In The Brain Reduced By Plant Flavonoid
Article Date: 21 May 2008 - 3:00 PDT
Researchers at the University of Illinois report this week
that a plant compound found in abundance in celery and green
peppers can disrupt a key component of the inflammatory
response in the brain. The findings have implications for
research on aging and diseases such as Alzheimer's and
multiple sclerosis.
The study appears this week in Proceedings of the National
Academy of Sciences.
Inflammation can be a blessing or a blight. It is a critical
part of the body's immune response that in normal
circumstances reduces injury and promotes healing. When it
goes awry, however, the inflammatory response can lead to
serious physical and mental problems.
Inflammation plays a key role in many neurodegenerative
diseases and also is implicated in the cognitive and
behavioral impairments seen in aging.
The new study looked at luteolin (LOO-tee-OH-lin), a plant
flavonoid known to impede the inflammatory response in several
types of cells outside the central nervous system. The purpose
of the study was to determine if luteolin could also reduce
inflammation in the brain, said animal sciences professor and
principal investigator Rodney Johnson.
"One of the questions we were interested in is whether
something like luteolin, or other bioactive food components,
can be used to mitigate age-associated inflammation and
therefore improve cognitive function and avoid some of the
cognitive deficits that occur in aging," Johnson said.
The researchers first studied the effect of luteolin on
microglia. These brain cells are a key component of the immune
defense. When infection occurs anywhere in the body, microglia
respond by producing inflammatory cytokines, chemical
messengers that act in the brain to orchestrate a whole-body
response that helps fight the invading microorganism.
This response is associated with many of the most obvious
symptoms of illness: sleepiness, loss of appetite, fever and
lethargy, and sometimes a temporary diminishment of learning
and memory. Neuroinflammation can also lead some neurons to
self-destruct, with potentially disastrous consequences if it
goes too far.
Graduate research assistant Saebyeol Jang studied the
inflammatory response in microglial cells. She spurred
inflammation by exposing the cells to lipopolysaccharide
(LPS), a component of the cell wall of many common bacteria.
Those cells that were also exposed to luteolin showed a
significantly diminished inflammatory response. Jang showed
that luteolin was shutting down production of a key cytokine
in the inflammatory pathway, interleukin-6 (IL-6). The effects
of luteolin exposure were dramatic, resulting in as much as a
90 percent drop in IL-6 production in the LPS-treated cells.
"This was just about as potent an inhibition as anything we
had seen previously," Johnson said.
But how was luteolin inhibiting production of IL-6"
Jang began by looking at a class of proteins involved in
intracellular signaling, called transcription factors, which
bind to specific "promoter" regions on DNA and increase their
transcription into RNA and translation into proteins.
Using electromobility shift assays, which measure the
binding of transcription factors to DNA promoters, Jang
eventually determined that luteolin inhibited IL-6
production by preventing activator protein-1 (AP-1) from
binding the IL-6 promoter.
AP-1 is in turn activated by JNK, an upstream protein kinase.
Jang found that luteolin inhibited JNK phosphorylation in
microglial cell culture. The failure of the JNK to activate
the AP-1 transcription factor prevented it from binding to
the promoter region on the IL-6 gene and transcription came
to a halt.
To see if luteolin might have a similar effect in vivo, the
researchers gave mice luteolin-laced drinking water for 21
days before injecting the mice with LPS.
Those mice that were fed luteolin had significantly lower
levels of IL-6 in their blood plasma four hours after
injection with the LPS. Luteolin also decreased LPS-induced
transcription of IL-6 in the hippocampus, a brain region that
is critical to spatial learning and memory.
The findings indicate a possible role for luteolin or
other bioactive compounds in treating neuroinflammation,
Johnson said.
"It might be possible to use flavonoids to inhibit JNK and
mitigate inflammatory reactions in the brain," he said.
"Inflammatory cytokines such as interleukin-6 are very well
known to inhibit certain types of learning and memory that are
under the control of the hippocampus, and the hippocampus is
also very vulnerable to the insults of aging," he said. "If
you had the potential to decrease the production of
inflammatory cytokines in the brain you could potentially
limit the cognitive deficits that result."
----------------------------
Article adapted by Medical News Today from original press
release. Source: Diana Yates University of Illinois at
Urbana-Champaign
----------------------------
http://www.eurekalert.org/pub_releases/2007-08/apa-nrs080807.-
php
New research shows how chronic stress worsens
neurodegenerative disease course Interventions can prevent or
halt stress-related inflammation that aggravate
neurodegenerative disease, study shows
SAN FRANCISCO - The evidence is accumulating on how bad stress
is for health. Chronic stress can intensify inflammation and
increase a person's risk for developing central nervous system
infections, neurodegenerative diseases, like multiple
sclerosis (MS), and other inflammatory diseases, say
researchers presenting at the 115th Annual Convention of the
American Psychological Association (APA). These researchers
have demonstrated for the first time that stress- related
increases in central nervous system inflammation are behind
the adverse effects of stress in an animal model of MS.
Researchers from Texas A & M University used mice to show what
role social stress plays in the immune process to influence
the course of an MS-like disease. They proposed that
stress-induced increases of pro- inflammatory cytokines, which
are proteins that regulate immune and inflammatory functions,
inhibit the clearing of a virus and allow the inflammatory
process to run amok. Stress, say the authors, may interact
with viral infections to increase vulnerability to diseases
such as MS. Meta-analysis of studies investigating the impact
of stressful events in patients with MS show an increased risk
of worsening symptoms of the disease.
In a series of experiments on mice, the authors showed that
increases in a particular cytokine - interleukin-6 (IL-6),
which is released during stress and regulates the part of the
immune system that fights infection - can make socially
stressed mice vulnerable to MS-like illnesses.
The researchers used a social disruption model (SDR) to
simulate social stress for mice and then infected the mice
with Theiler's murine encephalomyelitis (TMEV). Infection with
TMEV results in an acute infection of the central nervous
system followed by a chronic autoimmune disease similar to
that seen in humans with MS. Their laboratory has previously
shown that exposure to social stress prior to infection
exacerbates both the early viral infection and the later
autoimmune demyelinating MS-like phase of the disease.
To create a stressful environment, researchers housed three
young male mice together for several weeks. After the mice
established a stable social hierarchy, researchers introduced
an older aggressive male into the residence for a couple of
hours. The intruder exhibits aggressive behavior - posturing,
fighting, wounding, pursuit - that results in submissive
behaviors and social defeat in the younger resident mice. This
procedure was repeated for three consecutive nightly two-hour
sessions with one night off, followed by an additional three
nightly sessions. To keep the mice from getting used to the
intruder, a new intruder was introduced for each session.
What they found was this stress appears to elevate levels of
IL-6, which subsequently increases the severity of the MS-like
illness. Furthermore, using specific IL-6 neutralizing
antibody treatments during the stress exposure can prevent the
stress-related worsening of the disease, said the authors.
In one experiment, they showed that mice exposed to social
disruption had elevated central and peripheral levels of
IL-6. However, infusing the neutralizing antibody into the
brain prevented this stress-induced increase in IL-6. This
demonstrated that the antibody could effectively reverse
the stress-related increases in IL-6 in brain and in
circulating blood.
----------------------------
Molecule May Drive Multiple Sclerosis-Linked Disorder
Discovery could lead to treatments for transverse
myelitis and MS
WEDNESDAY, Oct. 12 (HealthDay News) -- Researchers report that
a single molecule called IL-6 is the cause of transverse
myelitis (TM), an autoimmune disease in the central nervous
system that's related to multiple sclerosis.
The study found that levels of IL-6 are dramatically elevated
in the spinal fluid of people with TM. The finding may help in
the development of treatments for both TM and multiple
sclerosis.
This is the first time a single culprit has been identified as
causing a CNS (central nervous system) autoimmune disease,"
researcher Dr. Adam Kaplin, a psychiatrist and assistant
professor of medicine at Johns Hopkins University School of
Medicine, said in a prepared statement.
IL-6 is a chemical messenger that immune system cells use to
communicate with each other. Most TM patients suffer a single
attack, but 15 percent to 30 percent of TM patients go on to
develop full- blown multiple sclerosis. TM usually results in
permanent impairment, including leg and arm weakness, bowel
and bladder dysfunction, pain and paralysis.
The researchers decided to investigate IL-6 because TM
patients suffer from memory impairment and depression.
Previous research implicated IL-6 in mood and concentration
disorders.
The study appears in the October issue of the Journal of
Clinical Investigation.
The U.S. National Institute of Neurological Disorders and
Stroke has more about transverse myelitis.
-- Robert Preidt
SOURCE: Johns Hopkins Medicine, news release, news release,
Sept. 22, 2005
Last Updated: Oct. 12, 2005
Copyright =A9 2005 ScoutNews LLC. All rights reserved
--------------------------------------------------------------
<<snip>> IL6-induced BBB defect precipitates iron
accumulation <<snip>>
J Neuropathol Exp Neurol. 1998 Mar;57(3):268-82. Related
Articles, Links
Abnormal iron deposition associated with lipid peroxidation in
transgenic mice expressing interleukin-6 in the brain.
Castelnau PA, Garrett RS, Palinski W, Witztum JL, Campbell IL,
Powell HC.
Department of Pathology (Neuropathology), School of Medicine,
University of California San Diego and the Veterans Affairs
Research Service, La Jolla 92093-0612, USA.
Transgenic mice, named GFAP-IL6, that express interleukin-6 in
astrocytes in the central nervous system (CNS) have a
constitutive blood-brain barrier (BBB) defect and develop a
progressive neurodegenerative disease. Based on
ultrastructural observations showing electron-dense pigment in
the brain of the GFAP-IL6 mice, we hypothesized that iron
metabolism was altered in the brains of these animals.
Enhanced histochemical methods revealed abnormal iron
deposition in the cerebellum from 1 month of age that worsened
with progression of the disease. Immunohistochemical analysis
of iron-binding proteins (IBP) showed increased ferritin
immunoreactivity and a decreased signal from the transferrin
receptor in symptomatic animals. Atomic absorption
spectroscopy revealed a 40% increase of total iron
concentration in the cerebellum at the symptomatic stage. In
order to obtain evidence that accumulation of this oxidizing
metal was toxic, we looked for the presence of oxidative
damage. Using the MAL-2 antibody, extensive lipid peroxidation
(LP) was detected in the neocortex and the cerebellum in
symptomatic animals. Ultrastructural analysis indicated
lipofuscin deposition at the sites of neuro-axonal
degeneration and abnormal iron deposition. These results
suggest that the IL6-induced BBB defect precipitates iron
accumulation in the GFAP-IL6 mouse brain and that subsequent
IBP regulation mediates protective responses. As these
defenses become overwhelmed, the iron overload seems to
promote LP, which may contribute to the neurodegeneration that
ensues. This transgenic mouse model of IL6-mediated
neurodegeneration provides a unique opportunity to examine
several aspects of iron metabolism in the brain, including its
entry at the site of the BBB, its distribution through the
IBP, and its mechanisms of toxicity.
PMID: 9600219 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
--------------= =AD=AD-----
Who loves ya. Tom
Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
Article Date: 21 May 2008 - 3:00 PDT
Researchers at the University of Illinois report this week
that a plant compound found in abundance in celery and green
peppers can disrupt a key component of the inflammatory
response in the brain. The findings have implications for
research on aging and diseases such as Alzheimer's and
multiple sclerosis.
The study appears this week in Proceedings of the National
Academy of Sciences.
Inflammation can be a blessing or a blight. It is a critical
part of the body's immune response that in normal
circumstances reduces injury and promotes healing. When it
goes awry, however, the inflammatory response can lead to
serious physical and mental problems.
Inflammation plays a key role in many neurodegenerative
diseases and also is implicated in the cognitive and
behavioral impairments seen in aging.
The new study looked at luteolin (LOO-tee-OH-lin), a plant
flavonoid known to impede the inflammatory response in several
types of cells outside the central nervous system. The purpose
of the study was to determine if luteolin could also reduce
inflammation in the brain, said animal sciences professor and
principal investigator Rodney Johnson.
"One of the questions we were interested in is whether
something like luteolin, or other bioactive food components,
can be used to mitigate age-associated inflammation and
therefore improve cognitive function and avoid some of the
cognitive deficits that occur in aging," Johnson said.
The researchers first studied the effect of luteolin on
microglia. These brain cells are a key component of the immune
defense. When infection occurs anywhere in the body, microglia
respond by producing inflammatory cytokines, chemical
messengers that act in the brain to orchestrate a whole-body
response that helps fight the invading microorganism.
This response is associated with many of the most obvious
symptoms of illness: sleepiness, loss of appetite, fever and
lethargy, and sometimes a temporary diminishment of learning
and memory. Neuroinflammation can also lead some neurons to
self-destruct, with potentially disastrous consequences if it
goes too far.
Graduate research assistant Saebyeol Jang studied the
inflammatory response in microglial cells. She spurred
inflammation by exposing the cells to lipopolysaccharide
(LPS), a component of the cell wall of many common bacteria.
Those cells that were also exposed to luteolin showed a
significantly diminished inflammatory response. Jang showed
that luteolin was shutting down production of a key cytokine
in the inflammatory pathway, interleukin-6 (IL-6). The effects
of luteolin exposure were dramatic, resulting in as much as a
90 percent drop in IL-6 production in the LPS-treated cells.
"This was just about as potent an inhibition as anything we
had seen previously," Johnson said.
But how was luteolin inhibiting production of IL-6"
Jang began by looking at a class of proteins involved in
intracellular signaling, called transcription factors, which
bind to specific "promoter" regions on DNA and increase their
transcription into RNA and translation into proteins.
Using electromobility shift assays, which measure the
binding of transcription factors to DNA promoters, Jang
eventually determined that luteolin inhibited IL-6
production by preventing activator protein-1 (AP-1) from
binding the IL-6 promoter.
AP-1 is in turn activated by JNK, an upstream protein kinase.
Jang found that luteolin inhibited JNK phosphorylation in
microglial cell culture. The failure of the JNK to activate
the AP-1 transcription factor prevented it from binding to
the promoter region on the IL-6 gene and transcription came
to a halt.
To see if luteolin might have a similar effect in vivo, the
researchers gave mice luteolin-laced drinking water for 21
days before injecting the mice with LPS.
Those mice that were fed luteolin had significantly lower
levels of IL-6 in their blood plasma four hours after
injection with the LPS. Luteolin also decreased LPS-induced
transcription of IL-6 in the hippocampus, a brain region that
is critical to spatial learning and memory.
The findings indicate a possible role for luteolin or
other bioactive compounds in treating neuroinflammation,
Johnson said.
"It might be possible to use flavonoids to inhibit JNK and
mitigate inflammatory reactions in the brain," he said.
"Inflammatory cytokines such as interleukin-6 are very well
known to inhibit certain types of learning and memory that are
under the control of the hippocampus, and the hippocampus is
also very vulnerable to the insults of aging," he said. "If
you had the potential to decrease the production of
inflammatory cytokines in the brain you could potentially
limit the cognitive deficits that result."
----------------------------
Article adapted by Medical News Today from original press
release. Source: Diana Yates University of Illinois at
Urbana-Champaign
----------------------------
http://www.eurekalert.org/pub_releases/2007-08/apa-nrs080807.-
php
New research shows how chronic stress worsens
neurodegenerative disease course Interventions can prevent or
halt stress-related inflammation that aggravate
neurodegenerative disease, study shows
SAN FRANCISCO - The evidence is accumulating on how bad stress
is for health. Chronic stress can intensify inflammation and
increase a person's risk for developing central nervous system
infections, neurodegenerative diseases, like multiple
sclerosis (MS), and other inflammatory diseases, say
researchers presenting at the 115th Annual Convention of the
American Psychological Association (APA). These researchers
have demonstrated for the first time that stress- related
increases in central nervous system inflammation are behind
the adverse effects of stress in an animal model of MS.
Researchers from Texas A & M University used mice to show what
role social stress plays in the immune process to influence
the course of an MS-like disease. They proposed that
stress-induced increases of pro- inflammatory cytokines, which
are proteins that regulate immune and inflammatory functions,
inhibit the clearing of a virus and allow the inflammatory
process to run amok. Stress, say the authors, may interact
with viral infections to increase vulnerability to diseases
such as MS. Meta-analysis of studies investigating the impact
of stressful events in patients with MS show an increased risk
of worsening symptoms of the disease.
In a series of experiments on mice, the authors showed that
increases in a particular cytokine - interleukin-6 (IL-6),
which is released during stress and regulates the part of the
immune system that fights infection - can make socially
stressed mice vulnerable to MS-like illnesses.
The researchers used a social disruption model (SDR) to
simulate social stress for mice and then infected the mice
with Theiler's murine encephalomyelitis (TMEV). Infection with
TMEV results in an acute infection of the central nervous
system followed by a chronic autoimmune disease similar to
that seen in humans with MS. Their laboratory has previously
shown that exposure to social stress prior to infection
exacerbates both the early viral infection and the later
autoimmune demyelinating MS-like phase of the disease.
To create a stressful environment, researchers housed three
young male mice together for several weeks. After the mice
established a stable social hierarchy, researchers introduced
an older aggressive male into the residence for a couple of
hours. The intruder exhibits aggressive behavior - posturing,
fighting, wounding, pursuit - that results in submissive
behaviors and social defeat in the younger resident mice. This
procedure was repeated for three consecutive nightly two-hour
sessions with one night off, followed by an additional three
nightly sessions. To keep the mice from getting used to the
intruder, a new intruder was introduced for each session.
What they found was this stress appears to elevate levels of
IL-6, which subsequently increases the severity of the MS-like
illness. Furthermore, using specific IL-6 neutralizing
antibody treatments during the stress exposure can prevent the
stress-related worsening of the disease, said the authors.
In one experiment, they showed that mice exposed to social
disruption had elevated central and peripheral levels of
IL-6. However, infusing the neutralizing antibody into the
brain prevented this stress-induced increase in IL-6. This
demonstrated that the antibody could effectively reverse
the stress-related increases in IL-6 in brain and in
circulating blood.
----------------------------
Molecule May Drive Multiple Sclerosis-Linked Disorder
Discovery could lead to treatments for transverse
myelitis and MS
WEDNESDAY, Oct. 12 (HealthDay News) -- Researchers report that
a single molecule called IL-6 is the cause of transverse
myelitis (TM), an autoimmune disease in the central nervous
system that's related to multiple sclerosis.
The study found that levels of IL-6 are dramatically elevated
in the spinal fluid of people with TM. The finding may help in
the development of treatments for both TM and multiple
sclerosis.
This is the first time a single culprit has been identified as
causing a CNS (central nervous system) autoimmune disease,"
researcher Dr. Adam Kaplin, a psychiatrist and assistant
professor of medicine at Johns Hopkins University School of
Medicine, said in a prepared statement.
IL-6 is a chemical messenger that immune system cells use to
communicate with each other. Most TM patients suffer a single
attack, but 15 percent to 30 percent of TM patients go on to
develop full- blown multiple sclerosis. TM usually results in
permanent impairment, including leg and arm weakness, bowel
and bladder dysfunction, pain and paralysis.
The researchers decided to investigate IL-6 because TM
patients suffer from memory impairment and depression.
Previous research implicated IL-6 in mood and concentration
disorders.
The study appears in the October issue of the Journal of
Clinical Investigation.
The U.S. National Institute of Neurological Disorders and
Stroke has more about transverse myelitis.
-- Robert Preidt
SOURCE: Johns Hopkins Medicine, news release, news release,
Sept. 22, 2005
Last Updated: Oct. 12, 2005
Copyright =A9 2005 ScoutNews LLC. All rights reserved
--------------------------------------------------------------
<<snip>> IL6-induced BBB defect precipitates iron
accumulation <<snip>>
J Neuropathol Exp Neurol. 1998 Mar;57(3):268-82. Related
Articles, Links
Abnormal iron deposition associated with lipid peroxidation in
transgenic mice expressing interleukin-6 in the brain.
Castelnau PA, Garrett RS, Palinski W, Witztum JL, Campbell IL,
Powell HC.
Department of Pathology (Neuropathology), School of Medicine,
University of California San Diego and the Veterans Affairs
Research Service, La Jolla 92093-0612, USA.
Transgenic mice, named GFAP-IL6, that express interleukin-6 in
astrocytes in the central nervous system (CNS) have a
constitutive blood-brain barrier (BBB) defect and develop a
progressive neurodegenerative disease. Based on
ultrastructural observations showing electron-dense pigment in
the brain of the GFAP-IL6 mice, we hypothesized that iron
metabolism was altered in the brains of these animals.
Enhanced histochemical methods revealed abnormal iron
deposition in the cerebellum from 1 month of age that worsened
with progression of the disease. Immunohistochemical analysis
of iron-binding proteins (IBP) showed increased ferritin
immunoreactivity and a decreased signal from the transferrin
receptor in symptomatic animals. Atomic absorption
spectroscopy revealed a 40% increase of total iron
concentration in the cerebellum at the symptomatic stage. In
order to obtain evidence that accumulation of this oxidizing
metal was toxic, we looked for the presence of oxidative
damage. Using the MAL-2 antibody, extensive lipid peroxidation
(LP) was detected in the neocortex and the cerebellum in
symptomatic animals. Ultrastructural analysis indicated
lipofuscin deposition at the sites of neuro-axonal
degeneration and abnormal iron deposition. These results
suggest that the IL6-induced BBB defect precipitates iron
accumulation in the GFAP-IL6 mouse brain and that subsequent
IBP regulation mediates protective responses. As these
defenses become overwhelmed, the iron overload seems to
promote LP, which may contribute to the neurodegeneration that
ensues. This transgenic mouse model of IL6-mediated
neurodegeneration provides a unique opportunity to examine
several aspects of iron metabolism in the brain, including its
entry at the site of the BBB, its distribution through the
IBP, and its mechanisms of toxicity.
PMID: 9600219 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
--------------= =AD=AD-----
Who loves ya. Tom
Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk