This is for JR and Susan.

I started on it yesterday. So I won't take out what J already posted.

Is YOUR PSOR immune system ANGRY at YOU?

Sounds like a plausible theory considering the emotional high's and
low's of psor ville.

But we know your emotions and a dozen other things trigger psoriasis.
So
why doesn't everyone get flaky skin then?

This NEXT GUY is kicking some PSOR FAT and chewing it at the same
time.
http://endocrinology.ucsd.edu/Faculty/olefsky.html

Will Dr. Jerrold Olefsky chew the LPS right outa that FAT?

His most recent study of 430 studies, right here and right NOW.

WOW......

www.ncbi.nlm.nih.gov/pubmed/19883619
Hematopoietic Cell-Specific Deletion of Toll-like Receptor 4
Ameliorates Hepatic and Adipose Tissue Insulin Resistance in High-Fat-
Fed Mice.

Saberi M, Woods NB, de Luca C, Schenk S, Lu JC, Bandyopadhyay G, Verma
IM, Olefsky JM.

Department of Medicine, Division of Endocrinology and Metabolism,
University of California, San Diego, La Jolla, CA 92093, USA.

Chronic low-grade inflammation, particularly in adipose tissue, is an
important modulator of obesity-induced insulin resistance. The Toll-
like receptor 4 (Tlr4) is a key initiator of inflammatory responses in
macrophages. We performed bone marrow transplantation (BMT) of Tlr4lps-
del or control C57Bl/10J donor cells into irradiated wild-type C57Bl6
recipient mice to generate hematopoietic cell-specific Tlr4 deletion
mutant (BMT-Tlr4(-/-)) and control (BMT-WT) mice. After 16 weeks of a
high-fat diet (HFD), BMT-WT mice developed obesity, hyperinsulinemia,
glucose intolerance, and insulin resistance. In contrast, BMT-Tlr4
(-/-) mice became obese but did not develop fasting hyperinsulinemia
and had improved hepatic and adipose insulin sensitivity during
euglycemic clamp studies, compared to HFD BMT-WT controls. HFD BMT-Tlr4
(-/-) mice also showed markedly reduced adipose tissue inflammatory
markers and macrophage content. In summary, our results indicate that
Tlr4 signaling in hematopoietic-derived cells is important for the
development of hepatic and adipose tissue insulin resistance in obese
mice.

PMID: 19883619

http://en.wikipedia.org/wiki/Haematopoietic_stem_cell
http://en.wikipedia.org/wiki/Haematopoiesis
http://en.wikipedia.org/wiki/TLR4
http://en.wikipedia.org/wiki/Lipopolysaccharide
http://en.wikipedia.org/wiki/Endotoxin

http://en.wikipedia.org/wiki/Lymphocyte_antigen_96
Symbols LY96; MD-2

----

md-2  (look at the jpg in the LPS wiki link above)

http://www.ncbi.nlm.nih.gov/pubmed/10359581
MD-2, a molecule that confers lipopolysaccharide responsiveness on
Toll-like receptor 4.
Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M.

Department of Immunology, Saga Medical School, Saga, Japan.

Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila
Toll, a leucine-rich repeat molecule that can trigger innate responses
against pathogens. The TLR4 gene has recently been shown to be mutated
in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to
lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS.
However, transfection of TLR4 does not confer LPS responsiveness on a
recipient cell line, suggesting a requirement for an additional
molecule. Here, we report that a novel molecule, MD-2, is requisite
for LPS signaling of TLR4. MD-2 is physically associated with TLR4 on
the cell surface and confers responsiveness to LPS. MD-2 is thus a
link between TLR4 and LPS signaling. Identification of this new
receptor complex has potential implications for understanding host
defense, as well as pathophysiologic, mechanisms.

PMID: 10359581 [PubMed - indexed for MEDLINE]

----

So the psor brew isn't complete without MD-2?

And drinking brew 102 will make your psor so much sorer. :(

I know. It's like reading the SFB abstract and putting the facts
together to come
to a contusion. LOL

And you know how my conclusions bruise your brain cells JR? <G>

----------

But,

OK, so will a TLR4 antagonist help psoriatics?

Off the top of my psor head, i'd say YES.

READ how Olefsky put two and two together to subtract TLR4's from LPS?

And what does LPS have to do with this immunity equation for folks on
AUTO?

EASY, by slowing TLR4, then LPS isn't going to cause the Th1 skew.

STILL, i'd rather slow it from gut translocation with sweet whey. :)

I'm so sweet. :)   LOL

I'll even repost the article that J posted to go with the above
abstract ::

Isn't it odd how they hardly resemble each other?  LOL

Maybe tomorrow i'll look at the hpa-axis and stress in relationship to
it?

nah...

http://www.eurekalert.org/pub_releases/2009-11/cp-hsf102809.php
How saturated fatty acids 'anger' the immune system (and how to stop
them)

Researchers have new evidence to explain how saturated fatty acids,
which soar in those who are obese, can lead the immune system to
respond in ways that add up to chronic, low-grade inflammation. The
new results could lead to treatments designed to curb that
inflammatory state, and the insulin resistance and type 2 diabetes
that come with it.

One key, according to the report in the November Cell Metabolism, a
Cell Press publication, is an immune receptor (called Toll-like
receptor 4 or Tlr4) at the surface of blood cells, including a
particularly "angry" class of macrophages known to pump out toxic
molecules and spur inflammation. It now appears that fatty acids may
in essence "hijack" those immune cells via Tlr4.

"Tlr4 is out there to sense bacterial products, but one of those looks
a lot like fatty acids," said the study's senior author Jerrold
Olefsky of the University of California, San Diego. "They don't know
it's not bacteria."

That bacterial product is something called lipopolysaccharide (LPS)
found in bacterial membranes. Olefsky notes, however, that they have
not yet fully demonstrated that fatty acids bind Tlr4 directly.

Scientists had suspected that Tlrs might be the "sensors" linking
obesity to inflammation. Indeed, earlier studies had supported that
notion. In the new study, the researchers show that this interaction
is particularly important in the bloodstream. Mice lacking Tlr4 only
in blood cells grew obese when they were fed a high-fat diet, but they
were largely spared the metabolic consequences of their obesity. The
mice were fat, but metabolically they continued to "look pretty
normal," Olefsky said.

The researchers showed in another Cell Metabolism report last year
that a "genetic trick" designed to kill off the offending macrophages,
which are distinguished by a CD11c marker, could reverse insulin
resistance in obese mice. The method used by the team wasn't one that
they could consider translating into the clinic, however (http://
www.eurekalert.org/pub_releases/2008-10/cp-ki093008.php).

The new findings suggest one that could. "A Tlr4 antagonist – now
that's a therapeutic," Olefsky said. "The jury is still out, but it
sure makes sense they could be a new class of insulin sensitizers."

They say that drugs aimed at Tlr4 have already been developed, and the
idea that those drugs may hold promise in fighting insulin resistance
and type 2 diabetes is one Olefsky's team is now exploring in detail
in the mice.

###

The researchers include Maziyar Saberi, University of California, San
Diego, La Jolla, CA; Niels-Bjarne Woods, The Salk Institute for
Biological Studies, La Jolla, CA; Carl de Luca, University of
California, San Diego, La Jolla, CA; Simon Schenk, University of
California, San Diego, La Jolla, CA; Juu Chin Lu, University of
California, San Diego, La Jolla, CA; Gautam Bandyopadhyay, University
of California, San Diego, La Jolla, CA; Inder M. Verma, The Salk
Institute for Biological Studies, La Jolla, CA; and Jerrold M.
Olefsky, University of California, San Diego, La Jolla, CA.

==================================

These anti TLR4 drugs could pay a FAT dividend for LARD Butts and psor
HEADs???? LOL

But why hasn't someone reported on it already?

Is this CRX-526 drug running around out there?

www.ncbi.nlm.nih.gov/pubmed/15879143
A synthetic TLR4 antagonist has anti-inflammatory effects in two
murine models of inflammatory bowel disease.

Fort MM, Mozaffarian A, Stöver AG, Correia Jda S, Johnson DA, Crane
RT, Ulevitch RJ, Persing DH, Bielefeldt-Ohmann H, Probst P, Jeffery E,
Fling SP, Hershberg RM.

Corixa Corporation, Seattle, WA 98101, USA.

Current evidence indicates that the chronic inflammation observed in
the intestines of patients with inflammatory bowel disease is due to
an aberrant immune response to enteric flora. We have developed a
lipid A-mimetic, CRX-526, which has antagonistic activity for TLR4 and
can block the interaction of LPS with the immune system. CRX-526 can
prevent the expression of proinflammatory genes stimulated by LPS in
vitro. This antagonist activity of CRX-526 is directly related to its
structure, particularly secondary fatty acyl chain length. In vivo,
CRX-526 treatment blocks the ability of LPS to induce TNF-alpha
release. Importantly, treatment with CRX-526 inhibits the development
of moderate-to-severe disease in two mouse models of colonic
inflammation: the dextran sodium sulfate model and multidrug
resistance gene 1a-deficient mice. By blocking the interaction between
enteric bacteria and the innate immune system, CRX-526 may be an
effective therapeutic molecule for inflammatory bowel disease.

PMID: 15879143

AT the very least, if this drug does nothing for psoriasis, we can
spend a lot more time looking at SFB (segmented filamentous bacterium)
for
PSOR cure clues.

Wouldn't SFB prove that Th17 is due to sFB and the Th1 skew isn't a
FACTOR?

Or ASS BIG a factor?  <w>

I'd think so.

I'll run a trial and not let any of you know. LOL

Kiddding but will you get it anyway?   <G>

Let's see what i can find for crx-526.

CRX-526 is a synthetic lipid A mimetic molecule, also known as an
aminoalkyl-glucosaminide-phosphate (AGP)

Guilty.

When it intersects hPa and it always does i'll keep
you on your toes.

What is the end all and BE ALL of psoriasis and most autoimmune
conditions ruled by Th17?

It's in YOUR GUT.  So susan, is your gut uPstream of HPA and cortisol?

Why not?

I've said this for HOW many YEARS now?

Only 8 in this group. :(

But i've lived it for how many in the real world?

More then I like to think.

I've fought my way from 70% pasi at times down to nearly zero.

And even now i worry that heart disease still looms.

I want to CURE me.

And you by default. LOL

Sure I love you.

But, not as much as I LOVE ME.   <g>

So you ask what is this gut trip?

EASY... do what i say and eat sweet whey. :)

Duh..

http://www.wellnessresources.com/health/articles/how_fiber_friendly_f...
How Fiber & Friendly Flora Reduce Inflammation

Wednesday, November 04, 2009 - Byron Richards, CCN

Scientists have made a major breakthrough in understanding why dietary
fiber and friendly GI tract flora (acidophilus) provide significant
benefit to such inflammatory problems as colitis, asthma, and
arthritis.

Dietary fiber is fermented in the lower colon by friendly flora,
resulting in the production of short chain fatty acids (SCFAs).  The
new discovery is that SCFAs bind on to a receptor on immune cells
called G-protein-coupled receptor 43 (GPR43).

The scientist showed that when GPR43 is activated by the SCFAs then
inflammation is controlled.  And conversely, their experiments showed
that when GPR43 is not activated then inflammation persists.  This is
an extremely important discovery.

It means that if you have adequate dietary fiber and friendly flora
then you have an intestinal “rain forest” that is producing enough of
the short chain fatty acids to help regulate immune cells to not
produce excessive inflammatory signals.

On the other hand, diets high in sugar and other forms of junk will
create an imbalance in the gut, as will repeated use of antibiotics.
True enough, this situation promotes an overgrowth of hostile bacteria
(like H. Pylori) or Candida albicans.  However, there is more to it.
The lack of production of SCFAs due to the imbalanced condition is an
additional source of inflammation.  The inflammation then weakens the
digestive lining, making it easier for the hostile inhabitants to gain
a foothold and wreak further harm.

It is now correct to view both dietary fiber and friendly flora as
anti-inflammatory nutrition, not just for the digestive tract but as a
possible factor in any problem of ongoing inflammation (including knee
joints).  I have repeatedly fixed serious inflammatory problems in
infants and children by fixing their digestive tracts – now I
understand a key aspect explaining why this works.

==============

OK so much for Houdini randallisms that no body seems to accept for
yin/yang reasons aPParently. LOL

What do i care?

I'm out to CURE me first anyway.

Duh, don't be a dumbell here.

Let's start with something esoteric yet germane.

FoxP3 perhaPs?

Exactly...

www.ncbi.nlm.nih.gov/pubmed/19880293
Polymorphisms in the FOXP3 gene in Han Chinese psoriasis patients.

Gao L, Li K, Li F, Li H, Liu L, Wang L, Zhang Z, Gao T, Liu Y.

Department of Dermatology of Xijing Hospital, Fourth Military Medical
University, Xi'an 710032, Shaanxi, China.

BACKGROUND: Psoriasis is a common dermatological disorder, in which
autoimmunity plays an important role. CD4(+)CD25(+) regulatory T cells
(T-regs) have been suggested to be involved in the pathogenesis of
some autoimmune diseases. T-regs express the fork head/winged helix
transcription factor, FOXP3, which appears to be of key importance in
the development and function of T-regs. Studies have found that single-
nucleotide polymorphisms (SNPs) in the FOXP3 gene contribute to
susceptibility to some autoimmune disorders. However, information
about FOXP3 gene in psoriasis is limited. OBJECTIVE: This study
evaluated the association between FOXP3 gene SNPs and susceptibility
to psoriasis in a Han Chinese population. METHODS: In a hospital-based
case-control study, 524 patients with psoriasis and 549 psoriasis-free
controls were recruited according to age and gender. We investigated
four SNPs in the FOXP3 gene (-6054, deletion/ATT; -3279, A/C; -924, A/
G; IVS9+459, A/G) in psoriatic patients, and assessed allele and
genotype frequencies in psoriatic patients (237 females, 287 males)
and normal controls (272 females, 277 males). The polymorphisms were
genotyped using the PCR sequence-specific primer (PCR-SSP) technique
and PCR-restriction fragment length polymorphism (RFLP) analysis.
RESULTS: We found that increased risk of psoriasis was associated with
the FOXP3 -3279 AC genotype (adjusted OR, 1.32; 95% CI, 1.01-1.74) and
the combined AC+AA genotype (adjusted OR, 1.38; 95% CI, 1.07-1.78),
compared with the -3279 CC genotype. We also found that an increased
risk of psoriasis was associated with the FOXP3 IVS9+459 GG genotype
(adjusted OR, 2.24; 95% CI, 1.41-3.58). However, the combined GA+GG
genotype showed no such tendency (adjusted OR=1.28; 95% CI,
1.00-1.64), compared with the IVS9+459 AA genotype. There was no
evidence of an increased risk associated with the FOXP3-6054 deletion/
ATT or FOXP3-924 A/G genotype. In combined genotype analyses, the
FOXP3-3279 AC+AA genotype was more obviously associated in males
(adjusted OR=1.60, 95% CI=1.11-2.31) and severe psoriasis patients
(PASI score >20; adjusted OR=1.97, 95% CI=1.41-2.75). Meanwhile, the
FOXP3 IVS9+459 GA+GG genotype was also associated with severe
psoriasis patients (adjusted OR=1.69, 95% CI=1.21-2.36). CONCLUSIONS:
FOXP3 polymorphisms appear to contribute to the risk of psoriasis in a
Han Chinese population. Larger studies are needed to confirm these
findings.

PMID: 19880293

FOXp3 again?

YeP and with Treg's (T-reg's) in the next article.

HOW important are tREG'?

WEll that is one of the autoimmune conundrums.

Not enough TREG's or to much Th17?

Which i believe Th17 leves are due to SFB.

So let's nail this Psor PuPPy down which ever it is.

www.newscientist.com/article/dn18096-injected-cells-stop-body-from-at...
Injected cells stop body from attacking self

18:24 03 November 2009 by Jessica Hamzelou

A virtually unlimited supply of rare cells can now be produced in the
laboratory to fight diseases such as rheumatoid arthritis in mice.

Crucially, these cells, which dampen down the body's immune response,
have been engineered so that they target damaged tissue yet don't
leave the rest of the body open to infection.

Vaccines have long harnessed the body's natural ability to fight
disease. Therapies that boost our natural immune response to cancer
are also in the works (see Autoimmune disease cells harnessed to fight
cancer).
SEE: http://www.newscientist.com/article/dn18075-autoimmune-disease-cells-...
[or see the last article in this thread]

But in autoimmune disease – in which the immune system mistakenly
attacks the body's own tissue – the opposite is needed. So
immunologists have long eyed up the cells that dampen down the immune
response, known as regulatory T-cells or T-regs, for their potential
to treat autoimmune disorders such as rheumatoid arthritis, diabetes
and multiple sclerosis.

There have been two challenges: how to obtain large supplies of the
rare T-regs, which make up less than 1 per cent of all immune cells,
and how to neutralise dangerous immune cells without weakening the
entire immune system, leaving people open to infection. Now Hans
Stauss and his colleagues at University College London have made a
stab at solving both.

Straight to the joint
The team starts by extracting ordinary T-cells – immune cells that are
common in the blood – from mice and using a virus to insert two genes
into these cells. One gene, FOXP3, transforms the ordinary T-cells
into T-regs. The second gene codes for a receptor for a substance
called ovalbumin.

Next the researchers injected ovalbumin into mice with rheumatoid
arthritis, which is caused by normal T-cells attacking cartilage. Each
mouse had two arthritic joints, but the researchers injected the
ovalbumin into one only. Then they injected the lab-produced T-reg
cells into the same mice.

The idea was that the ovalbumin would attract the cells, which would
dampen down the arthritic inflammation that was attacking the joint's
cartilage. The rest of the immune system, however, would remain
intact.

Sure enough, the injected cells homed in on the ovalbumin-injected
arthritic joints and reduced inflammation, while the other joints
remained inflamed.

More targets
Stauss says that a similar T-reg therapy could be developed to target
autoimmune diseases that strike other parts of the body, by adding
genes for receptors specific to molecules found there.