SKIN Ai GWAS -- JG Krueger & SKIN - Th17 (IL-17) - CCL20 - LPS- IL-10- IL-22 - LL-37- HeParin- Vit D3 -Treg's - IDO- IFN- FoxP3
randall
GWAS info on Ai...(autoimmune~ :)
http://en.wikipedia.org/wiki/Genome-wide_association_study
In genetic epidemiology, a genome-wide association study (GWA study,
or GWAS) - also known as whole genome association study (WGA study) -
is an examination of genetic variation across a given genome, designed
to identify genetic associations with observable traits. In human
studies, this might include traits such as blood pressure or weight,
or why some people get a disease or condition.[1]
<sniP>
Get a GWAS grant from the NIH:
http://grants.nih.gov/grants/gwas/
http://www.genengnews.com/news/bnitem.aspx?name=71883369
Investigators Find Genetic Basis to Clustering Effect Seen in
Autoimmune Diseases
GEN News Highlights
Scientists at Stanford University School of Medicine have uncovered a
genetic basis for why people with a particular autoimmune disease are
often predisposed to another autoimmune disease. Their research also
demonstrated that two such clusters tend to be mutually exclusive.
The study is published online December 24 in PLoS Genetics. It is
titled “Autoimmune disease classification by inverse association with
SNP alleles”.
Pairs of autoimmune diseases have been linked in clinical practice.
For example, people with type 1 diabetes are at a higher risk for
autoimmune thyroid disease. However, no one has ever known why these
clusters exist, the Stanford team points out.
Atul Butte, M.D., Ph.D., assistant professor of pediatrics and of
biomedical informatics and the study's senior author, and his
colleagues looked at data from about six genome-wide association
studies conducted on patients with or without autoimmune diseases
including type 1 diabetes, rheumatoid arthritis, multiple sclerosis,
autoimmune thyroid disease, and ankylosing spondylitis.
The investigators focused on the 573 SNPs that were examined in each
of the six published studies. They found 15 that predisposed an
individual to several autoimmune diseases. To their surprise, they
found nine locations that conferred a heightened risk of certain
autoimmune diseases but reduced risk of getting certain others.
For instance, a particular chemical unit at an SNP site shown to
predispose people to multiple sclerosis also rendered them, as a
group, more likely to have autoimmune thyroid disease. On the other
hand, an alternative chemical unit at the same site predisposed them
to rheumatoid arthritis and ankylosing spondylitis. Additionally,
people predisposed to one pair of diseases were protected against the
other.
“Maybe we should stop considering all autoimmune diseases in one
lumped category,” remarks Dr. Butte, who is also the director of the
Center for Pediatric Bioinformatics at Lucile Packard Children's
Hospital. “It looks as if there may be at least two different kinds.
“Several of these nine interesting SNPs we've found are located in or
near genes that code for molecules found on cell surfaces,” Dr. Butte
continues, making them potentially easier targets for drug
development.
<sniP>
-------
http://newswire.rockefeller.edu/?page=engine&id=1014
Posted: December 23, 2009
Genomic differences identified in common skin diseases
It’s sometimes said that dermatologists do one of two things (though
it’s not dermatologists who say it): Faced with a skin disease that’s
too dry, they try to wet it; if the disease is too wet, they try to
dry it. There’s some wisdom in this general approach, says James G.
Krueger, head of the Laboratory for Investigative Dermatology at
Rockefeller University. But it also suggests the lack of sophisticated
treatments for many skin conditions. “A hairdryer or a sponge doesn’t
make a very good therapeutic. We need to do better. We need to be more
specific.”
In experiments published this month in The Journal of Allergy and
Clinical Immunology, Krueger and colleagues drilled down on the
molecular nitty-gritty that distinguishes the two most common forms of
inflammatory skin disease, atopic eczema and psoriasis. The
researchers say that the ability to distinguish between the disorders’
genetic and immunological signatures opens the door for more narrowly
targeted therapies sorely needed by the millions of people afflicted
worldwide.
A team of researchers led by Visiting Fellow Emma Guttman and Research
Associate Mayte Suárez-Fariñas used extensive genetic tests to detail
the gene expression patterns in skin samples of both diseases and
normal skin. They also dissected the activity that each of the
diseases jump-starts in the immune system, defining the unique
signaling molecules — called cytokines — that T cells produce in the
face of each threat to direct the immune response. The scientists
confirmed previously recognized immunological distinctions, but they
found even more remarkable differences in the expression of genes that
control the differentiation of skin cells, establishing a new paradigm
for precisely classifying the diseases.
Atopic eczema is a disease that chronically inflames and irritates
patches of skin, often causing “wet” lesions. It runs in families, is
associated with respiratory allergies such as asthma and afflicts
about 100 million people worldwide, up to 25 percent of some
populations of children. Psoriasis, which is also chronic and usually
produces red and scaly “dry” rashes, is even more prevalent, striking
two to three percent of people around the world. The diseases
generally do not respond to the same treatments, except for systemic
immune suppression, which becomes dangerous if prolonged and is not
approved by the Food and Drug Administration. Other existing
treatments are inadequate, Guttman says.
Earlier genetic testing of eczema and psoriasis did not use enough
samples to produce the statistical power needed to definitively
establish how each disease differs from normal skin, the researchers
say. Up to this point, scientists have focused in particular on a
defect in one gene associated with some cases of eczema — filaggrin.
Filaggrin, however, is only one of 150 to 200 genes that comprise the
epidermal differentiation complex, which directs the formation of the
skin’s defensive barriers and cell growth more generally. The new
research shows that the expression of many of these genes is
suppressed in eczema, especially in those genes responsible for
producing the hard, insoluble envelope surrounding skin cells. One
gene, loricrin, is expressed at only two percent of its level in
normal skin. Psoriasis, by contrast, generally increases the
expression of many of these genes, the researchers found.
Until now, animal models have guided the development of new therapies
for human skin disorders. However, it has been difficult to determine
if a model simulates psoriasis, atopic eczema or some other
inflammatory disorder. And so far, treatments that have shown promise
in animals by and large have not translated to humans. The new
research may be a game-changer. “What we’ve got is a means to
critically evaluate the models of these diseases in animals in a way
that wasn’t possible before,” says Krueger, who is also director of
Rockefeller’s Milstein Medical Research Program.
By detailing the gene expression profile of each disease and zeroing
in on a key difference in how they operate at the molecular level, the
research also suggests new possibilities — narrow-acting
immunosuppression drugs or treatments for the barrier around skin
cells, for instance — that might strike individual vulnerabilities in
the diseases without harming the patients. “Atopic eczema is widely
prevalent and understudied. We’ve begun a process that may take years
to come to fruition, but this is where you start to look for better
treatment targets,” Krueger says. “You find the fundamental defects,
and that’s what we’ve done.”
<sniP>
The abstract to go with the above:
http://www.jacionline.org/article/S0091-6749(09)01432-8/abstract
or
www.ncbi.nlm.nih.gov/pubmed/20004782
2009 Dec;124(6):1235-1244.e58.
Broad defects in epidermal cornification in atopic dermatitis
identified through genomic analysis.
Guttman-Yassky E, Suárez-Fariñas M, Chiricozzi A, Nograles KE, Shemer
A, Fuentes-Duculan J, Cardinale I, Lin P, Bergman R, Bowcock AM,
Krueger JG.
Laboratory for Investigative Dermatology, Rockefeller University, New
York, NY 10065, USA.
BACKGROUND: Psoriasis and atopic dermatitis (AD) are common, complex
inflammatory skin diseases. Both diseases display immune infiltrates
in lesions and epidermal growth/differentiation alterations associated
with a defective skin barrier. An incomplete understanding of
differences between these diseases makes it difficult to compare human
disease pathology to animal disease models. OBJECTIVE: To characterize
differences between these diseases in expression of genes related to
epidermal growth/differentiation and inflammatory circuits. METHODS:
We performed genomic profiling of mRNA in chronic psoriasis (n = 15)
and AD (n = 18) skin lesions compared with normal human skin (n = 15).
RESULTS: As expected, clear disease classifications could be
constructed on the basis of expected immune polarity (T(H)1, T(H)2, T
(H)17) differences. However, even more striking differences were
identified in epidermal differentiation programs that could be used
for precise disease classifications. Although both psoriasis and AD
skin lesions displayed regenerative epidermal hyperplasia, which is a
general alteration in epidermal growth, keratinocyte terminal
differentiation was differentially polarized. In AD, we found
selective defects in expression of multiple genes encoding the
cornified envelope, with the largest alteration in loricrin (expressed
at 2% of the level of normal skin). At the ultrastructural level, the
cornified envelope in AD was broadly defective with highly decreased
compaction of corneocytes and reduced intercellular lipids. Hence, the
entire keratinocyte terminal differentiation program (cytoplasmic
compaction, cornification, and lipid release) is defective in AD,
potentially underlying the immune differences. CONCLUSION: Our study
shows that although alterations in barrier responses exist in both
diseases, epidermal differentiation is differentially polarized, with
major implications for primary disease pathogenesis.
PMID: 20004782
----------
Th-17 create IL-17
http://en.wikipedia.org/wiki/T_helper_17_cell
Transforming growth factor beta (TGF-β), interleukin 6 (IL-6),
interleukin 21 (IL-21) and interleukin 23 (IL-23) have been implicated
in mice and humans contribute to Th17 formation
http://en.wikipedia.org/wiki/T_helper_17_cell#Differentiation
[...]
In humans, a combination of TGF-β, IL-1β and IL-23 induces Th17
differentiation from naive T cells.[5] Both interferon gamma (IFNγ)
and IL-4, the main stimulators of Th1 and Th2 differentiation
respectively, have been shown to negatively regulate Th17
differentiation.
Functions
On initial characterisation, Th17 cells were broadly implicated in
autoimmune disease and auto-specific Th17 were shown to be highly
pathogenic. A more natural role for Th17 cells is suggested by studies
which have demonstrated preferential induction of IL-17 in cases of
host infection with various bacterial and fungal species. Th17
primarily produce two main members of the IL-17 family; IL-17A and
IL-17F which are involved in the recruitment, activation and migration
of neutrophils. These cells also secrete IL-21 and IL-22. Recently,
Th17 polarized cells have been shown to mediate the regression of
established tumors [9][10]. Whether the highly inflammatory nature of
Th17 cells is sufficient to cause or contribute to carcinogenesis is
the subject of current debate [11].
<sniP>
http://en.wikipedia.org/wiki/Interleukin_17
197 returns for Th-17 + IL-17 + psoriasis [groups]
http://groups.google.com/groups/search?hl=en&q=Th-17+IL-17+psoriasis&btnG=Search&sitesearch=groups.google.com
miP-3alPha (CCL20) + psoriasis [groups] 11 returns:
http://groups.google.com/groups/search?hl=en&q=mip-3alpha+psoriasis&sitesearch=
But 68 retruns for CCL20 in the P NG (psoriasis newsgroup)
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=ccl20
IL-10 (Th2 subset or skew) lowers CCL20
miP-3alPha -aka - CCL20
http://en.wikipedia.org/wiki/MIP-3_alpha
Chemokine (C-C motif) ligand 20 (CCL20) or liver activation regulated
chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a
small cytokine belonging to the CC chemokine family. It is strongly
chemotactic for lymphocytes and weakly attracts neutrophils.[1] CCL20
is implicated in the formation and function of mucosal lymphoid
tissues via chemoattraction of lymphocytes and dendritic cells towards
the epithelial cells surrounding these tissues. CCL20 elicits its
effects on its target cells by binding and activating the chemokine
receptor CCR6.[2]
Gene expression of CCL20 can be induced by microbial factors such as
lipopolysaccharide (LPS), and inflammatory cytokines such as tumor
necrosis factor and interferon-γ, and down-regulated by IL-10.[3]
CCL20 is expressed in several tissues with highest expression observed
in peripheral blood lymphocytes, lymph nodes, liver, appendix, and
fetal lung and lower levels in thymus, testis, prostate and gut.[1][4]
The gene for CCL20 (scya20) is located on chromosome 2 in humans.[5]
-----
New info on commensalism and LLR's coming out every day bringing light
to
these pathways
And understandings. :)
Will they fit randallistical Gi musings?
We don't care as long as there's a PSOR CURE. LOL
------------
We move towards the IL22 subset: (increased or Th1 skewings)
www.ncbi.nlm.nih.gov/pubmed/19731362
Eur J Immunol. 2009 Oct;39(10):2779-88.
IL-17 and IL-22 mediate IL-20 subfamily cytokine production in
cultured keratinocytes via increased IL-22 receptor expression.
Tohyama M, Hanakawa Y, Shirakata Y, Dai X, Yang L, Hirakawa S,
Tokumaru S, Okazaki H, Sayama K, Hashimoto K.
Department of Dermatology, Ehime University Graduate School of
Medicine, Shitsukawa, Toon-city, Ehime 791-0295, Japan. to...@m.ehime-
u.ac.jp
IL-20 cytokine subfamily members, including IL-19, IL-20, and IL-24,
are highly expressed in psoriatic skin lesions. Here, we demonstrate
that psoriasis mediators IL-17 and IL-22 synergistically induce the
production of IL-20 subfamily proteins in cultured human
keratinocytes. Interestingly, expression of the IL-22 receptor
(IL-22R) also increased in epidermal lesions versus normal skin.
IL-22R over-expression using an adenoviral vector to mimic psoriatic
conditions in cultured keratinocytes significantly enhanced IL-17- and
IL-22-induced production of IL-20 subfamily cytokines. Furthermore,
IL-17 and IL-22 coordinately enhanced MIP-3alpha, IL-8, and heparin-
binding EGF-like growth factor (HB-EGF) production, depending on the
amount of IL-22R expression. Additionally, because IL-20 and IL-24
share the IL-22R with IL-22, the function of IL-20 and IL-24 was also
increased. IL-20 and IL-24 have effects similar to that of IL-22;
IL-24 showed more potent expression than IL-20. A combination of IL-24
and IL-17 increased the production of MIP-3alpha, IL-8, and HB-EGF, as
did a combination of IL-22 and IL-17. These data indicate that
increased IL-22R expression in epidermal keratinocytes contributes to
the pathogenesis of psoriasis through enhancing the coordinated
effects of IL-22 and IL-17, inducing the production of the IL-20
subfamily, chemokines, and growth factors.
PMID: 19731362
So what the heck is mip-3alpha?
[see above as i cleared it up but not in the context of MANiPulating
it... LOL
miP-2alpha or CCL20 and heParin with IL-17 in regards to these
pathways?
Co-incidentally:
======================
While looking at IL-17 and psor with autoimmune in mind, in the news,
I searched it on the web and found this Art Ayers blog.
And i liked it.
Art says on his blog:
Nov. 12, 2008--->
http://coolinginflammation.blogspot.com/2009/11/psoriasis-il-17-cathelicidin-tlrs-nfkb.html
Psoriasis, IL-17, Cathelicidin, TLRs, NFkB, Inflammation and HeParin
TheraPy
Host DNA Released by Keratinocyte Apoptosis Binds LL-37 and Activates
Dendrocytes
Psoriasis is an inflammation of the skin that leads to overproduction
of keratinocytes resulting in a thick crust. Skin inflammation, in
this case, is considered a result of autoimmunity, but an autoantigen
has not been identified. It is more likely that psoriasis results
from an autoinflammatory condition, in which inflammation produces a
complex of self molecules that mimic bacterial DNA and trigger TLR/
NFkB inflammation signaling. And of course, if this is going to be
interesting, it has to involve heparin.
Vitamin D Binds to a Transcription Factor Receptor that Controls
Antimicrobial Peptides
A significant component of the innate immune system is a group of
antimicrobial peptide (defensins, cathelicidins, e.g. LL-37). These
short polypeptides owe their natural antibiotic activity to numerous
basic (positively charged, arginine and lysine) amino acids. The
transcription factor that controls the expression of these peptides is
the vitamin D receptor. Thus, various forms of vitamin D influence
the amount of antimicrobial peptides produced in the mouth, skin and
crypts of the intestinal villi. Oral vitamin D3 would be expected to
directly improve defensin production in the gut and LL-37 production
in the skin.
IL-17 Stimulates Skin Inflammation and LL-37 Production
A specific group of lymphocytes, called T helper 17 cells, produce
IL-17. These Th17 cells accumulate in some sites of inflammation,
such as psoriasis and their secretion of IL-17 is associated with
ongoing inflammation and may contribute to LL-37 production, as well
as apoptosis of keratinocytes in the thickening skin of psoriasis
plaques.
http://www.ncbi.nlm.nih.gov/pubmed/19623255?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_Discovery_PMC&linkpos=2&log$=citedinpmcarticles&logdbfrom=pubmed
Th17 Cells Are Produced in the Gut in Response to Segmented Bacteria
One of my readers brought to my attention an article that shows that
one of the hundreds of species of gut bacteria, segmented filamentous
baceria, stimulates the gut to develop T helper 17 cells that
subsequently migrate to sites of inflammation.
http://www.medpagetoday.com/Gastroenterology/InflammatoryBowelDisease/16472
This emphasizes the link between the gut and inflammatory diseases and
parallels other examples of gut influence on disease, such as the
ability of Helicobacter pylori to affect asthma or parasitic worms to
tame Crohn’s disease, allergies and asthma.
Inflammation Lowers Heparan Sulfate Production and Spreads LL-37
One of my students induced inflammation in cells in vitro and showed
by quantitative PCR that genes involved in heparan sulfate
proteoglycan production are selectively silenced. This observation
explains in part the loss of heparan sulfate in kidneys and intestines
that contributes to the leakiness of these organs in response to
inflammation and the partial repair of these organs by heparin
treatment. Decrease of heparan sulfate that normally coats cells and
binds antimicrobial peptides, such as LL-37, would explain the
enhanced movement of LL-37 in psoriatic skin.
LL-37 Binds to Host DNA and Triggers Toll-Like Receptors
DNA is released from keratinocytes in psoriatic skin and this host DNA
binds the antimicrobial peptide cathelicidin LL-37. The LL-37/DNA
complex mimics bacterial DNA and triggers the Toll-like receptors
(TLR) on the surface of immune cells, dendrocytes, to activate NFkB,
the transcription factor controlling inflammation.
Heparin Treats Psoriasis
It seemed obvious to me that the heparin binding domains (Look at all
the basic amino acids in blue in the illustration of LL-37.) of LL-37
were involved in DNA binding and the reason the LL-37 was binding to
host DNA, was that heparan sulfate had been depleted as a result of
local inflammation. It also seemed obvious that topical heparin
should eliminate psoriasis plaques. So I did a Google search of
psoriasis + topical heparin and got a hit on a 1991 patent application
that claims a broad applicability for heparin use in curing symptoms
of a wide variety of diseases, including psoriasis.
http://www.patentstorm.us/patents/5037810/description.html
[...]
And one of Art's readers said:
---
___E said... __
So ... this means avoiding oral Vitamin D3 .. ? //Erik
November 13, 2009 3:26 PM
Dr. Art Ayers said...
__E,__
The way that I read it, oral vit D3 should improve the production of
antimicrobial peptides (AMPs) and augment innate immunity. In most
cases, decreased AMPs is a problem. In rosacea, where the typical skin
AMP, LL-37, is cleaved to produce shorter peptides that contribute to
the inflammatory symptoms, then vit D both increases symptoms and
attacks the bacteria that are part of the problem. Thus, it appears
that in some cases vit D3 is needed in addition to appropriate
inhibitors of inflammation.
These are complex diseases that can't be cured by just manipulating
symptoms with drugs.
[...]
[then in response to a question or comment by Krissie]
SAID:
Dr. Art Ayers said...
Krissie,
I don't think that there is a down side to topical heparin therapy.
Long polysaccharides of heparan sulfate are secreted attached to
membrane bound proteins on most cells. Those molecules drag across the
surface and are taken in again (half life = six hours). The heparan is
degraded, the membrane proteins are recycled to the Golgi and new
heparan is attached. The point is that other proteins with heparin-
binding domains, as well as other heparin are also dragged in and
reprocessed. This reprocessing is why heparin injected into veins is
quickly removed and must be replenished to suppress the clotting
enzymes that all have heparin-binding domains.
The simple point is that heparin applied to the skin and to a great
extent, the gut, is trapped on the surface and metabolized. It is very
hard to increase serum heparin levels by eating heparin. Afterall,
your gut is coated with it, that is why it is a source of heparin.
Inadequate heparan sulfate is a sign of disease and is suggested by a
propensity for blood to clot or for female infertility remedied by
heparin injections.
My guess on why topical and oral heparin have not been developed is
that they would replace expensive, dangerous patented pharmaceuticals
with cheap, safe nutrichemicals. These approaches would eliminate the
need for a large part of the health industry.
The Anti-Inflammatory Diet and Lifestyle that I suggest is just a
compendium of dietary solutions to most of the sources of chronic
inflammation. Relief of chronic inflammation should revive heparan
sulfate production.
<sniP>
I like this ART Ayers.
I'll find another aPPlicable page:
Here's a good one if you think your gut is art of the Ai situation.
http://coolinginflammation.blogspot.com/2009/11/biofilms-as-human-gut-mycorrhizals.html
Biofilms as Human Gut Mycorrhizals
Are Biofilms Healthy Extensions of Intestinal Villi?
If soil is the stomach of the earth, then plant roots and mycorrizal
fungi must be the intestines.
Mycorrhizal fungal hyphae extend from root hairs of plants into
surrounding soil and enhance the uptake of phosphate and other
nutritents. Many plants cannot colonize new soil without taking their
fungal partners with them. It would seem obvious that the highly
adapted human gut flora would include bacteria and fungi that actively
communicate with intestinal epithelial cells. Perhaps that
communication includes both nutrients, e.g. hydrogen, ammonia, etc.,
vitamins and bacterial wall components, e.g. LPS.
Plants Sit and Mine Soil, Humans Mine Nutrients Passed through Their
Gut
I want to try to give a plant’s view of human digestion. Plants
elaborate roots that branch repeatedly and the final extensions sprout
hairs from individual epithelial cells. Mycorrhizal fungal hyphae
further extend the reach of the plant into the soil for nutrients.
I think that a plant would look at us and see us stuffing soil/food
into our mouths and watch it come out the other end. It would then
try to figure out where are roots are, i.e. how we absorb the water
and minerals from our moving internal stream of soil. The villi of
the small intestines would look like root hairs, but where are the
mycorrhizal fungi? Another problem is that the soil keeps moving past
the root hairs and would break off fungal hyphae extending into the
soil. Still another problem is the constant shedding of epithelial
cells from the tips of the villi. The plant would be perplexed, but
closer inspection would reveal that biofilms could solve the problems.
Biofilms Coat the Intestinal Villi
Biofilms coating and perhaps spanning the villi of the small
intestines may enhance the transport of nutrients into the villi.
This may be controversial and the biofilms may be more commonly
limited to the smoother surface of the colon. The point here is that
biofilms may enhance the intestinal uptake of nutrients from food.
Biofilms may, therefore, be essential for health and extend the reach
of the intestinal epithelial cells.
Bacterial Community Composition May Be Determined by Diet
A biofilm is composed of some type of linear polymer, such as DNA,
heparan sulfate or bacterial acidic polysaccharides, with bacteria
that bind to the polymer and to the intestinal epithelium. Diet
determines the bacterial composition of the biofilm. Thus, the
newborn starts without biofilms, gut development is finished by growth
hormones in milk and a single species of Bifidobacteria excludes
biofilm production, until solid food or formula initiates adult
biofilms. The bacteria in the biofilm depend on diet, so the biofilms
can be either beneficial or pathogenic.
Communication within Biofilms and with the Intestines
The bacteria respond to the presence of other bacteria by quorum
sensing, which involves release of small molecules that alter the gene
expression of other bacteria in the community. As a consequence,
genes, e.g. antibiotic resistance, are exchanged and metabolism is
altered. This is how Klebsiella nitrogenase and hydrogen production
is controlled. The biofilm bacteria also produce compounds, e.g.
vitamin D (?), that alter the behavior of the intestinal epithelial
cells. The intestines can respond with inflammation to recognized
pathogen components or by triggering development of cells of the
immune system. The intestines are the home of most of the body’s
immune cells.
Stimulation of Tregs
Helicobacter pylori adhering to the stomach lining increases the
stomach’s quota of regulatory T cells that are involved in
immunological tolerance. Presumably, the supply of Tregs in the
intestines is also regulated by biofilms. Disruption of this system
by chronic inflammation can deplete Tregs and lead to unrestrained
immune attack that is observed as inflammatory bowel disease. Thus,
Crohn’s disease and ulcerative colitis may be triggered by damaged
biofilms.
<end post by art ayers>
Be sure to use his link for other health posts. :)
===========================================
http://www.eurekalert.org/pub_releases/2009-12/nlmc-npd122209.php
New pathway discovered that may prevent tissue damage resulting from
inflammation
Study could pave the way for new treatments for immune diseases
(New York, New York – December 22, 2009): Interferon gamma is a
protein secreted by lymphocytes that is used to fight the bacteria in
white blood cells that cause tuberculosis. In a study published this
week in Immunity, scientists at NYU Langone Medical Center have
discovered that in addition to white blood cells, other cells such as
epithelial and endothelial cells, also respond to interferon gamma and
also protect mice from uncontrolled tuberculosis infection. This new
pathway could lead to the developments of treatments that could limit
or prevent tissue damage resulting from inflammation.
"Through research on tuberculosis, we discovered a new way that the
immune system response is controlled," said lead author Joel Ernst,
MD, director of the Division of Infectious Diseases and the Jeffrey
Bergstein Professor of Medicine at NYU Langone Medical Center.
"Further study may reveal treatments that could be useful in control
of inflammation and tissue damage in certain infections and autoimmune
diseases."
In this study, researchers looked at interferon gamma responses in
epithelial and endothelial cells to control tuberculosis in mice.
Cells such as epithelial and endothelial cells were found to respond
to interferon gamma by producing an enzyme, indolelamine-2-3-
dioxygenase (IDO), that converts the amino acid tryptophan to products
called kynurenines. These kynurenines inhibit the production of Th17
cells, the lymphocytes that contribute to tissue-damaging
inflammation.
###
The study's co-author is Ludovic Desvignes, PhD of the Department of
Microbiology at NYU Langone Medical Center. The research was funded by
grants from the National Institute of Allergy and Infectious Diseases
of the National Institutes of Health in Bethesda, Maryland.
----
They misPPeled indolelamine-2-3-dioxygenase LOL
--->Lelamine.?.. <w>
Let's see how many posts in the groups for INDOLEAMINE (IDO) not
indolelamine:: 20 returns
http://groups.google.com/groups/search?hl=en&q=indoleamine+psoriasis&sitesearch=
H'mm only 17 of those are mine?
LOL
Yep
http://groups.google.com/groups/search?hl=en&q=indoleamine+psoriasis+randall&sitesearch=
IDO catabolizes tryptophan
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2111116/
http://en.wikipedia.org/wiki/Indoleamine_2,3-dioxygenase
Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO EC 1.13.11.52) is an
immunomodulatory enzyme produced by some alternatively activated
macrophages and other immunoregulatory cells (also used as an immune
subversion strategy by many tumors).
Interferon-gamma (IFNG; MIM 147570) has an antiproliferative effect on
many tumor cells and inhibits intracellular pathogens such as
Toxoplasma and Chlamydia, at least partly because of the induction of
indoleamine 2,3-dioxygenase (INDO; EC 1.13.11.42). This enzyme
catalyzes the degradation of the essential amino acid L-tryptophan to
N-formylkynurenine.[supplied by OMIM][1]
IDO is the first and rate-limiting enzyme of Tryptophan catabolism
through kynurenine pathway, thus causing depletion of tryptophan which
can cause halted growth of microbes as well as T cells.
It catalyzes conversion of L-tryptophan to N-formylkynurenine.
-----
So make good gut flora and create a slightly acidic milieu in the
colon and get haPPy...
use the wit kit and diet for 30 days. :)
I'm adding in > L. Plantarum lacti bugs in to my next implant.
Only the second time i'm doing this SKIN saving procedure and to prove
if
Plantarum will lower SFB's in the ileaum (ileal) region.
Already ate kimchi for a week and noticed a distinct effect.
============
Ok, back to the pathways....
As long as we're on IFN let's hook it uP?
What?
With that scientist123FOXP3 guy?
Oh yes please.
www.ncbi.nlm.nih.gov/pubmed/20026056
Biochem Biophys Res Commun. 2009 Dec 17.
IL-6 and IFN-alpha from dsRNA-stimulated dendritic cells control
expansion of regulatory T cells.
Kubota N, Ebihara T, Matsumoto M, Gando S, Seya T.
Department of Microbiology and Immunology.
Foxp3(+) CD4(+) regulatory T cells (Treg) control not only
autoimmunity but also the effective immune response against RNA virus
infections, which produces virus-derived double-stranded RNA (dsRNA).
To induce effective anti-viral immunity, it is a key issue to learn
how Treg respond to dsRNA in vitro and in vivo. We here showed that
synthetic dsRNA, polyI:C, caused peripheral expansion of functional
Treg in a TICAM-1- and IL-6-dependent manner in vivo. PolyI:C did not
expand Treg directly, but promoted the expansion of naturally
occurring Treg indirectly through IL-6 produced from dendritic cells
(DCs). In addition, the expansion of Treg by IL-6 was inhibited by IFN-
alpha from polyI:C-stimulated DCs. These data suggest that the balance
of IL-6 and IFN-alpha in the region of RNA virus infection may
determine the number of peripheral Treg, which affects the effective
immune responses against viruses.
PMID: 20026056
Is there a real viral component to psoriasis or is it only LL37 and
self DNA making
the IL22 subset and Autoimmunity?
And what ever that means?
We depend on these REAL scientists to tell us.
Hope they hurry it up some. LOL
randall... haPPy XMAS 2009