Crohn's blamed on lazy immune cells
JRStern
response be so damaging? But, interesting.
J.
http://www.newscientist.com/article/mg20427354.000-crohns-blamed-on-lazy-immune-cells.html
Crohn's blamed on lazy immune cells
19 November 2009 by Linda Geddes
Magazine issue 2735.
A MYSTERIOUS bowel disease thought to be caused by an over-exuberant
immune system may paradoxically be triggered by immune cells that
don't do enough in the early stages of bacterial infection.
Since some treatments for Crohn's disease aim to suppress the immune
system, it's possible these drugs could be making things worse. The
discovery by Anthony Segal of University College London and his
colleagues is causing a stir among immunologists. Caetano Reis e Sousa
at Cancer Research UK calls it "provocative", while Jean-Laurent
Casanova at The Rockefeller University in New York says it is "a major
breakthrough".
A similar mechanism may be at the root of a host of other "autoimmune"
disorders, in which immune cells turn on the body's own tissue.
Underactive immune cells could also explain why some of us are more
prone to infectious diseases.
About 1 in 1000 people in the US and Europe have Crohn's. Symptoms
include swollen, painful intestines and diarrhoea. Inflamed sections
of gut often have to be surgically removed.
Segal and his colleagues got their first clue when they noticed a
weaker immune response in people with Crohn's than in healthy people
after both groups were injected with heat-killed Escherichia coli. The
team reasoned that this lukewarm response might allow an infection to
build up and eventually trigger a debilitating secondary immune
response, resulting in Crohn's.
If this is the case, though, why does Crohn's only manifest itself in
the intestine? After further experiments it became clear that the
immune weakness only revealed itself when large numbers of killed E.
coli were injected. As the bowel is one of the few places in the body
where bacteria exist in huge numbers, Segal concluded that this is
where the weakened immune response has its biggest impact. "It's only
in the bowel that you routinely get massive loads of bacteria - and if
these breach the intestinal wall it will cause an infection."
It still wasn't clear, however, what caused the weakened immunity in
the first place. So Segal's team focused on cells called macrophages,
the immune system's whistle-blowers. In people with Crohn's disease,
they found that macrophages secrete lower levels of cytokines, the
chemicals that rally other immune cells to infection sites (Journal of
Experimental Medicine, DOI: 10.1084/jem.20091683).
The team concluded that ineffectual rallying of immune cells in people
with defective macrophages is what allows intestinal bacteria to run
amok in the early stages of an infection, setting in motion the series
of events that leads to Crohn's disease.
Now Segal would like to look at the role of defective macrophages in
other autoimmune diseases, such as rheumatoid arthritis and psoriasis.
Casanova suspects that they may also leave people more susceptible to
illnesses such as tuberculosis. "Macrophages are central to many
physiological processes," he adds.
randall
> Barely more than informed speculation - why should the further immune
> response be so damaging? But, interesting.
I'll get out my specula and let you know what i find....
Oh crap i'm seeing myself in that mirror...
Must bend over perhaPs?
For WHAT?
http://en.wikipedia.org/wiki/Speculum_(medical)
Doesn't this also bring uP *speculum-colon-izations*?
How many colon real i zations in the psor group?
I can find a dozen. LOL
>
> J.
>
> http://www.newscientist.com/article/mg20427354.000-crohns-blamed-on-l...
>
> Crohn's blamed on lazy immune cells
> 19 November 2009 by Linda Geddes
> Magazine issue 2735.
>
> A MYSTERIOUS bowel disease thought to be caused by an over-exuberant
> immune system may paradoxically be triggered by immune cells that
> don't do enough in the early stages of bacterial infection.
Wouldn't it be due to colons leaking LPS and a subsequent Th1 skew?
Been my theory since JRStern posted the link to Xoma's bacterial lps--
good article.
Want to read it again?
It's in the group.
>
> Since some treatments for Crohn's disease aim to suppress the immune
> system, it's possible these drugs could be making things worse.
Gosh, do they mean biologicials or bio ILL logicals, that cause
brain cancer (PML)?
Are those crohn's folks being screwed even worse by big pharma
then psor skin folks?
How would we know.
Easy.... find how many died from PML and compare which are
psoriatics and which are crohn's folks.
They push bio ill logicals down both of us.... duh.
> The
> discovery by Anthony Segal of University College London and his
> colleagues is causing a stir among immunologists. Caetano Reis e Sousa
> at Cancer Research UK calls it "provocative", while Jean-Laurent
> Casanova at The Rockefeller University in New York says it is "a major
> breakthrough".
OK, i'll find the abstract after my cursory commentary on this
speculative post. :)
>
> A similar mechanism may be at the root of a host of other "autoimmune"
> disorders, in which immune cells turn on the body's own tissue.
> Underactive immune cells could also explain why some of us are more
> prone to infectious diseases.
Let me get this straight. We leak LPS due to a alkaline colon that
was designed to be slightly acidic and full of lacti loving bacteria
(good flora) and when it leaks to much LPS (endogenous endotoxin--
cell walls) you blame your BIG MAC's for not eating the CRAP?
That is good. I've used so many turbo charger supplements to do just
that I said SCREW IT. LOL
WE must find the promised land via homeostatic ville. :)
>
> About 1 in 1000 people in the US and Europe have Crohn's. Symptoms
> include swollen, painful intestines and diarrhoea. Inflamed sections
> of gut often have to be surgically removed.
And wait to look at what i find in pubmed.
It will be shocking.
How do i know?
Easy, i know they don't KNOW. LOL
>
> Segal and his colleagues got their first clue when they noticed a
> weaker immune response in people with Crohn's than in healthy people
> after both groups were injected with heat-killed Escherichia coli. The
> team reasoned that this lukewarm response might allow an infection to
> build up and eventually trigger a debilitating secondary immune
> response, resulting in Crohn's.
>
> If this is the case, though, why does Crohn's only manifest itself in
> the intestine? After further experiments it became clear that the
> immune weakness only revealed itself when large numbers of killed E.
> coli were injected. As the bowel is one of the few places in the body
> where bacteria exist in huge numbers, Segal concluded that this is
> where the weakened immune response has its biggest impact. "It's only
> in the bowel that you routinely get massive loads of bacteria - and if
> these breach the intestinal wall it will cause an infection."
What? Is this funny or am i cracking uP? LOL
>
> It still wasn't clear, however, what caused the weakened immunity in
> the first place
They should read that cayce guy. LOL
Cayce went in to a trance and made romance with your colon i zations.
http://en.wikipedia.org/wiki/Edgar_Cayce
He should have been a crap-o-logist. Maybe he was in another life
time?
>. So Segal's team focused on cells called macrophages,
> the immune system's whistle-blowers.
Let's see how many hits for little old me and BIG MAC's?
Over 500 hits,
http://groups.google.com/groups/search?hl=en&q=macrophages+psoriasis+randall&btnG=Search&sitesearch=
So there are only 499 returns.
But there are 15 BIG MAC's and at least one of those won't have
macrophage(s) in it. LOL
http://groups.google.com/groups/search?hl=en&q=big+mac+psoriasis+randall&sitesearch=
Are your BIG MAC's SMACKING DOWN on those LPS cell walls running wild
from YOUR'
LEAKY colon?
Take sweet whey and grow some lacti loving flora and get things REAL
again. LOL
> In people with Crohn's disease,
> they found that macrophages secrete lower levels of cytokines, the
> chemicals that rally other immune cells to infection sites (Journal of
> Experimental Medicine, DOI: 10.1084/jem.20091683).
>
> The team concluded that ineffectual rallying of immune cells in people
> with defective macrophages is what allows intestinal bacteria to run
> amok in the early stages of an infection, setting in motion the series
> of events that leads to Crohn's disease.
Man these guys do speculumate BIG time. LOL
>
> Now Segal would like to look at the role of defective macrophages in
> other autoimmune diseases, such as rheumatoid arthritis and psoriasis.
> Casanova suspects that they may also leave people more susceptible to
> illnesses such as tuberculosis. "Macrophages are central to many
> physiological processes," he adds.
Shall I give Segal a little lesson in colon realizations?
OK
It aPPears to be a teachable moment.
Hey.... is Segal the primary or what? **
www.ncbi.nlm.nih.gov/pubmed/19907654
Diminished macrophage apoptosis and reactive oxygen species generation
after phorbol ester stimulation in Crohn's disease.
Palmer CD, Rahman FZ, Sewell GW, Ahmed A, Ashcroft M, Bloom SL,
**___Segal AW___, Smith AM.
Department of Medicine, Centre for Molecular Medicine, University
College London, London, UK.
BACKGROUND: Crohn's Disease (CD) is a chronic relapsing disorder
characterized by granulomatous inflammation of the gastrointestinal
tract. Although its pathogenesis is complex, we have recently shown
that CD patients have a systemic defect in macrophage function, which
results in the defective clearance of bacteria from inflammatory
sites. METHODOLOGY/PRINCIPAL FINDINGS: Here we have identified a
number of additional macrophage defects in CD following diacylglycerol
(DAG) homolog phorbol-12-myristate-13-acetate (PMA) activation. We
provide evidence for decreased DNA fragmentation, reduced
mitochondrial membrane depolarization, impaired reactive oxygen
species production, diminished cytochrome c release and increased IL-6
production compared to healthy subjects after PMA exposure. The
observed macrophage defects in CD were stimulus-specific, as normal
responses were observed following p53 activation and endoplasmic
reticulum stress. CONCLUSION: These findings add to a growing body of
evidence highlighting disordered macrophage function in CD and, given
their pivotal role in orchestrating inflammatory responses, defective
apoptosis could potentially contribute to the pathogenesis of CD.
PMID: 19907654
OK, didn't think about the mitochondrial membrane thingy. <W>
If it brings LL37 (LL-37) in to the psor equation then we have
genius something as Gilliet/Lande say it's in ER region and
ushered in my Vitamin D3, hence D3 and LL37 (natural
antibiotics) trigger autoimmunity.
But let's not segue to that.
What about the genes? JRSTERN is always all abut the PSOR genes..
Or is that aboot the genes up the crohn's pathway?
How aboot the boot up the BUM?
http://www.phgfoundation.org/news/4935/
New susceptibility loci associated with IBD
18 November 2009 | By Dr Gurdeep Sagoo |
Ulcerative colitis is a common form of inflammatory bowel disease
(IBD) and is a chronic condition affecting the colon; combined with
Crohn’s disease, it ______affects around 1 in 400 people in the
UK_____ (according to the National Association for Colitis and Crohn’s
Disease). Over the past two years, several genome wide association
studies (GWAS) have expanded the number of genetic factors implicated
in IBD pathogenesis, with 32 loci associated with Crohn’s disease and
17 associated with ulcerative colitis. Three research groups have
recently published new GWAS studies online in the journal Nature
Genetics identifying several new genetic variants.
[ randall note: the other guys above said::: **About 1 in 1000 people
in the US and Europe have Crohn's. Symptoms
include swollen, painful intestines and diarrhoea.** ? So which is
it? 1 in 400 or 1 in 1000? randall note over]
The study by Asano et al. [Asano et al. (2009) Nat Genet 15 November
doi:10.1038/ng.482] reports a two-stage study of Japanese subjects
with more than 1,000 ulcerative colitis patients and 3,000 controls.
Many SNPs in the MHC region on chromosome 6 showed strong association
with IBD. Fifteen SNPs outside this region showing strong association
were analysed and three novel susceptibility loci identified: the
FCGR2A immunoglobulin receptor gene, the SLC26A3 glycoprotein gene,
and a variant on chromosome 13q12.
The second publication by the UK IBD Genetics Consortium and the
Wellcome Trust Case Control Consortium 2 [Barrett et al. Nat Genet 15
November doi:10.1038/ng.483] looked at two independent sets of around
2,400 patients with ulcerative colitis and around 5,000 controls.
Three new positions on chromosomes 7, 16, and 20 showed significant
association with the disease, the authors identified LAMB1, CDH1, and
HNF4A as biologically plausible candidate genes in these regions.
The third publication by Imielinski et al. [Imielinski et al. Nat
Genet 15 November doi:10.1038/ng.489] reports a GWAS of more than
3,400 European patients with early-onset IBD and almost 12,000
European and North American controls. This study detected associations
at 23 of the 32 loci previously implicated in Crohn’s disease and 8 of
the 17 previously implicated in ulcerative colitis. It also identified
five novel early-onset IBD susceptibility loci on chromosomes 2, 10,
16, 19, and 22. Of the multiple genes in these regions, the authors
consider the immunomodulatory cytokine IL27 gene to be the most likely
candidate gene involved in disease susceptibility.
Comment: These three well-conducted GWAS papers provide robust
evidence for association between several new genetic variants and
susceptibility to IBD. Each study identifies biologically plausible
candidate genes involved in autoimmunity or the function of the
epithelium. For example, the FCGR2A gene is implicated in
susceptibility to other autoimmune diseases, and encodes a receptor
that is expressed on the surface of several immune cells, whilst the
IL27 gene encodes a cytokine which regulates immune cells, lending
further support to the idea that this immune pathway plays a key role
in causing intestinal inflammation. These susceptibility genes now
require extensive follow-up work to understand their role in the
processes that cause IBD, which may lead to new approaches in
developing treatments.
<sniP>
WE HAVE new IL-27 abstracts for psoriasis TODAY.
www.ncbi.nlm.nih.gov/pubmed/19924133
Possible Roles of IL-27 in the Pathogenesis of Psoriasis.
Shibata S, Tada Y, Kanda N, Nashiro K, Kamata M, Karakawa M, Miyagaki
T, Kai H, Saeki H, Shirakata Y, Watanabe S, Tamaki K, Sato S.
Faculty of Medicine, Department of Dermatology, University of Tokyo,
Tokyo, Japan.
The immunological significance of IL-27 has been reported and
discussed in various Th1/Th17-mediated inflammatory diseases. However,
its importance in psoriasis is unknown. We investigated
pathophysiological roles of IL-27 in psoriasis in this study. Serum
IL-27 levels in psoriatic patients were significantly higher than
those in healthy controls, and correlated with disease severity and
serum IFN-gamma levels. An immunohistochemical analysis revealed the
infiltration of IL-27-secreting cells in the papillary dermis of
psoriatic skin lesions but not in skin lesions with atopic dermatitis
or normal skin. Furthermore, IL-27 alone greatly induced in vitro
CXCL9, CXCL10, and CXCL11 production and tyrosine phosphorylation of
signal transducer and activator of transcription 1 in normal human
keratinocytes, while it suppressed the tumor necrosis factor-alpha-
induced production of IL-1alpha and CCL20. These results indicate that
IL-27 may promote the onset of psoriasis, while it may simultaneously
attenuate the expanded inflammation in this disease. Our results
implicate potential therapeutic effects of IL-27 for psoriasis.Journal
of Investigative Dermatology advance online publication, 19 November
2009; doi:10.1038/jid.2009.349.
PMID: 19924133
I could do a LONG post on this. But won't as IL-10 which balances Th1
skews is simpler to deal with. <G>
--------
kofi posted this in the life extension NG::
J Immunol. 2009 Aug 15;183(4):2435-43. Epub 2009 Jul 22.
http://www.ncbi.nlm.nih.gov/pubmed/19625647
IL-27 is a key regulator of IL-10 and IL-17 production by human CD4+
T
cells.
Murugaiyan G, Mittal A, Lopez-Diego R, Maier LM, Anderson DE, Weiner
HL.
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard
Medical School, Boston, MA 02115, USA.
Although the physiologic pathways that control regulatory T cells
(Foxp3-expressing regulatory T cells, IL-10-secreting Tr1 cells) and
Th17 cells in rodents have been defined, the factors that control
these
differentiation pathways in humans are not well understood. In this
study, we show that IL-27 promotes the differentiation of
IL-10-secreting Tr1 cells while inhibiting Th17 generation and
molecules
associated with Th17 function. Furthermore, IL-27 inhibits
IL-17-polarizing cytokines on dendritic cells, which in turn decrease
IL-17 secretion from T cells. Our results demonstrate that IL-27 plays
a
key role in human T cells by promoting IL-10-secreting Tr1 cells and
inhibiting Th17 cells and thus provides a dual regulatory mechanism
to
control autoimmunity and tissue inflammation.
PMID: 19625647
-----
Gosh does this mean that a colon that is full of lacti loving gut
bugs,
like what that mercola dude is pushing will make the immune system
work right?
Maybe. But the wit kit is better. <G>
What does mercola push in those probiotic pills?
I'll find it.
Dr. Mercola gets probiotical:
http://probiotics.mercola.com/probiotics-powder.html
[...]
With my new probiotic powder formulas, you receive a minimum of 66
billion beneficial bacteria in every serving.
[...]
Bifidobacterium lactis – a friendly bacteria often found in yogurt
that is known to help stimulate immune responses*
Lactobacillus acidophilus – guards the health of your entire
digestive tract*
Bifidobacterium longum – keeps your digestive system running
smoothly, and helps enhance your immune system*
Bifidobacterium bifidum – helps promote a healthy balance of flora in
your intestine.* What's more, this organism is especially helpful for
enhancing immune response*
Lactobacillus casei – works with other helpful organisms, and helps
to encourage the growth of other "good" bacteria*
Lactobacillus plantarum – helps to ensure that the nutrients in
vitamins and supplements are getting to your cells*
Lactobacillus salivarius – promotes your intestinal health and helps
support your oral health as well*
Lactobacillus rhamnosus – assists your elimination and occasional
intestinal discomfort by working to stabilize your intestinal
microflora*
Lactobacillus bulgarious – works with other Lactobacillus strains to
provide you a potential source of dietary antioxidants*
Bacillus Coagulans – helps enhance your intestinal health and
provides back-up for sporadic intestinal discomfort*
Kyo-Dophilus® blend – specially-cultured organisms right at home in
your digestive tract that are able to survive hostile stomach acid*
-----
Wow... his gun is bigger and has more ammo in it.
BUTT so WAT?
Take note...
=============================
OK, need more proof?
[randall note: the trick to those lacti loving gut bugs is growing
them and being on a diet to do that]
Back to GUT hunches and proof:::
This next one was already in the psor group:::
IFN-alpha regulates Toll-like receptor-mediated IL-27 gene expression
in human macrophages.
Pirhonen J, Sirén J, Julkunen I, Matikainen S.
Department of Viral Diseases and Immunology, National Public Health
Institute, Mannerheimintie 166, FI-00300, Helsinki, Finland.
jaana.pirho
IL-27 is a novel member of the IL-12 cytokine family. IL-27 has pro-
and anti-inflammatory properties, and it controls the responses of
adaptive immunity. It promotes the differentiation of naïve Th cells
and suppresses the effector functions of Th17 cells. Biologically
active IL-27 is a heterodimer composed of EBV-induced gene 3 (EBI3)
and p28 proteins. We report that TLR-dependent expression of IL-27 in
human macrophages is mediated by IFN-alpha. Stimulation of
macrophages
with agonists for TLR3 {polyinosinic:polycytidylic acid [poly(I:C)]},
TLR4 (LPS), or TLR7/8 (R848) results in concurrent expression of EBI3
and p28. The p28 expression is inhibited with neutralizing anti-IFN-
alpha antibodies. Unlike poly(I:C), LPS, and R848, TLR2 agonist (S)-
[2,3-bis(palmitoyloxy)-(2RS)-propyl]-N-palmitoyl-(R)-Cys-(S)-Ser(S)-
Lys4-OH trihydrochloride does not stimulate macrophages to produce
IFN-
alpha, and therefore, it is not able to turn on the expression of
p28.
There is an IFN-stimulated response element (ISRE) in the p28 gene
promoter. IFN-alpha enhances the expression of IFN regulatory factor
1
(IRF-1) in macrophages and induces binding of IRF-1 to the p28 ISRE
site. The data provide a mechanistic basis for the IFN-alpha-mediated
activation of IL-27. The data emphasize a role of IFN-alpha in immune
responses, which rely on the recognition of pathogens by TLRs.
PMID: 17684041
Why are these lacti loving gut bugs SO GOOD?
Easy they create a slightly acidic milieu and the hierarchy of good
and BAD flora.
Sort of like in society? LOL
http://en.wikipedia.org/wiki/Social_environment
www.ncbi.nlm.nih.gov/pubmed/18567760
The probiotic Lactobacillus acidophilus stimulates chloride/hydroxyl
exchange activity in human intestinal epithelial cells.
Borthakur A, Gill RK, Tyagi S, Koutsouris A, Alrefai WA, Hecht GA,
Ramaswamy K, Dudeja PK.
Section of Digestive Diseases and Nutrition, Department of Medicine,
University of Illinois at Chicago, and Jesse Brown Veterans Affairs
Medical Center, Chicago, IL 60612, USA.
Probiotics are viable nonpathogenic microorganisms that are considered
to confer health benefits to the host. Recent studies indicated that
some Lactobacillus species function as probiotics and have been used
as alternative treatments for diarrhea, which occurs due to increased
secretion, decreased absorption, or both. However, the direct effects
of probiotics on intestinal electrolyte absorption are not known.
Therefore, we examined the effects of Lactobacillus on luminal
chloride/hydroxyl (Cl(-)/OH(-)) exchange activity in human intestinal
epithelial cells. Postconfluent Caco-2 cells were treated with the
Lactobacillus species ____Lactobacillus acidophilus (LA)____,
Lactobacillus casei, Lactobacillus ____plantarum,____ or Lactobacillus
rhamnosus (LR) for 3 h at a multiplicity of infection of 50. Cl(-)/OH
(-) exchange activity was measured as 4,4'-diisothiocyanostilbene-2,
2'-disulfonic acid-sensitive (36)Cl uptake in base-loaded cells.
Treatment with live, but not heat-killed, LA and LR significantly
increased Cl(-)/OH(-) exchange activity (approximately 50%), whereas
other species were ineffective. Similarly, the conditioned medium
(supernatant) of live LA increased Cl(-)/OH(-) exchange. The ability
of LA or its conditioned culture medium to enhance Cl(-)/OH(-)
exchange activity was blocked by PI-3 kinase inhibition but was
unaffected by inhibition of mitogen-activated protein kinases.
Corresponding to the increased Cl(-)/OH(-) exchange activity, LA
treatment increased the surface expression of the apical anion
exchanger, _____SLC26A3_____ [Down Regulated in Adenoma (DRA)]. The
increased DRA membrane localization might contribute to the increased
Cl(-) absorption by LA. Our results suggest that LA secretes soluble
effector molecule(s) into the culture medium that stimulate apical Cl
(-)/OH(-) exchange activity via phosphatidylinositol-3 kinase mediated
mechanism.
PMID: 18567760
Hey, hey we've got slc26a3 to play wit. Not just a bunch of lacti
freaking good flora bugs, but genes in the game for
Th1 and Th2
===================
So much for that proof. LOL
Or so much for POOF the magic Cayce lives in a dream and eats lemon
blosoms in a land called
Shucks you want the real deaL?
http://www.youtube.com/watch?v=3OiOlnoyljk
-----
Cut the THC you ancient hiPPie relics...I'LL sic CARTMAN on YOU.
http://en.wikipedia.org/wiki/Die_Hippie,_Die
[...]
Cartman runs a 'pest control' service to rid the town of hippies,
people he feared and hated for most of the series, mainly because
"they smoke pot, wear crap and smell bad." Having studied hippies in
his quest to eradicate them, Cartman deduces the hippies are about to
start a music festival in South Park. His attempts to warn the town
council are futile, and he is arrested soon afterwards for imprisoning
63 hippies in his basement.
<sniP>
OK, back to real deals right inside your garden of paradise when the
colon is slightly acidic and
it's ALL REAL and your SKIN is CLEAR.
Let's take this tack...
I'll run the numbers that prove big pig pharma like big pig gov is
skewing THEIR interest and
giving it up the BUM to the little GUY.
lps + crohn's 107 returns pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=crohn's+lps&log$=activity
Take LPS out and you'll get 22,053 returns for crohn's.
Why so few for LPS?
Isn't it the one thing that ties crohn's and psoriasis together?
Guts (colon lamina propria) leaking LPS, meaning permeable due to
altered mucosal flora?
I don't get it.
Do you?
But you do get 167 returns for keywords: probiotics + crohn's - pubmed
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=crohn's+probiotics&log$=activity
Let's look at a recent one.
OK.
www.ncbi.nlm.nih.gov/pubmed/19890092
Evidence for a cross-talk between human neutrophils and Th17 cells.
Pelletier M, Maggi L, Micheletti A, Lazzeri E, Tamassia N, Costantini
C, Cosmi L, Lunardi C, Annunziato F, Romagnani S, Cassatella MA.
Department of Pathology, Section of General Pathology, University of
Verona, Verona, Italy;
Interleukin (IL)-17A and IL-17F are two of several cytokines produced
by T helper 17 cells (Th17) which are able to indirectly induce the
recruitment of neutrophils. Recently, human Th17 cells have been
phenotypically characterized and shown to express discrete chemokine
receptors, including CCR2 and CCR6. Herein, we show that highly
purified neutrophils cultured with IFNgamma plus LPS produce the CCL2
and CCL20 chemokines, the known ligands of CCR2 and CCR6,
respectively. Accordingly, supernatants from activated neutrophils
induced chemotaxis of Th17 cells, which was greatly suppressed by anti-
CCL20 and anti-CCL2 antibodies. We also discovered that activated Th17
cells could directly chemoattract neutrophils via the release of
biologically active CXCL8. Consistent with this reciprocal
recruitment, neutrophils and Th17 cells were found in gut tissue from
___Crohn's__ disease and synovial fluid from rheumatoid arthritis
patients. Finally, we report that, although human Th17 cells can
directly interact with freshly isolated or preactivated neutrophils
via GM-CSF, TNFalpha and IFNgamma release, these latter cells cannot
be activated by IL-17A and IL-17F, due to their lack of IL-17RC
expression. Collectively, our results reveal a novel chemokine-
dependent reciprocal cross-talk between neutrophils and Th17 cells,
which may represent a useful target for the treatment of chronic
inflammatory diseases.
PMID: 19890092
Gosh JRSTERN doesn't this Tie crohn's Th17 and psoriasis Th17 together
with those BIG mac's?
And also to th1 skews?
The only thing left is will segmented filamentous bacterium in the
ileal region prove a further
induction of Th17? And will SFB's also prove to be beneficial when
homeostatic due
to a slightly acidic colon full of lacti loving GUT FLORA.... see
mercola laundry list. LOL
===========
Do we need more speculum realizatons in this psor or crohn game?
www.ncbi.nlm.nih.gov/pubmed/19897959
Therapeutic options to modulate barrier defects in inflammatory bowel
disease.
Hering NA, Schulzke JD.
Department of General Medicine, Charité Center 10, Campus Benjamin
Franklin, Berlin, Germany.
In inflammatory bowel disease (IBD), epithelial barrier function is
impaired contributing to diarrhea by a leak flux mechanism and
perpetuating inflammation by an increased luminal antigen uptake. This
barrier of the intestinal epithelium is composed of the apical
enterocyte membrane and the epithelial tight junction (TJ) and can be
affected by TJ alterations, induction of epithelial apoptosis and
appearance of gross lesions like erosions or ulcers as well as by
accelerated transcytotic antigen uptake. TJ strands are reduced in
Crohn's disease (CD) and strand breaks appear. Several of the 24
claudins are concerned in CD as e.g. claudin-2, -5 and -8. The
epithelial apoptotic rate has also been shown to be elevated causing
focal lesions. As far as regulation is concerned, Th1 cytokines like
TNF-alpha and interferon-gamma are important for CD, while Th2
responses are dominated by interleukin (IL)-13 and TNF-alpha in
ulcerative colitis (UC). IL-13 does stimulate epithelial apoptosis as
well as upregulates claudin-2 in UC. Together with an IL-13-dependent
restitution arrest, this may explain why ulcer lesions are seen
already early in UC but only in advanced stages of CD. Luminal antigen
uptake occurs via TJ discontinuities, epithelial gross lesions and
endocytotically. Therapeutically, anti-inflammatory remedies as e.g.
TNF-alpha antibodies are most effective in improving active IBD and in
parallel repairing barrier function. Again, this is assumed to be due
to reduced cytokine release in active IBD, as a result of immune cell
apoptosis. However, other agents can also directly affect barrier
function. Glutamine is discussed as a candidate for barrier therapy
but has never been shown to have a direct barrier influence in CD,
although it is an important metabolic fuel for enterocytes and has
been shown to preserve barrier functions in laboratory models. Also,
probiotics and TGF-beta and have beneficial effects in models, but no
data exist on barrier repair in IBD. In contrast, zinc has been shown
to improve barrier function in CD, although the inherent mechanisms
are unknown. Finally, food components can strengthen the epithelial
barrier as for example the flavonoid quercetin which has been shown to
upregulate claudin-4 within the epithelial TJ.
PMID: 19897959
I wondered where the ZiNC cure for psor came from. LOL
But if the gut tract is A OK then i'm fairly sure you'll have enought
zinc
in your diet.
You might not have enough iodine. As folks need to top off with
unleaded fuel
(diet) full of zincy foods.
=============
OK, ok already...
So get this.
Zero hits for keywords: lps probiotics crohn's on pubmed:
--0--
But and this is a BIG ONE.
You get four hits for keywords: LPS FLORA + crohn's
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=crohn's+flora+lps&log$=activity
----
www.ncbi.nlm.nih.gov/pubmed/19664152
Exaggerated inflammatory response of primary human myeloid dendritic
cells to lipopolysaccharide in patients with inflammatory bowel
disease.
Baumgart DC, Thomas S, Przesdzing I, Metzke D, Bielecki C, Lehmann SM,
Lehnardt S, Dörffel Y, Sturm A, Scheffold A, Schmitz J, Radbruch A.
Department of Medicine, Division of Gastroenterology and Hepatology,
Charité Medical School of the Humboldt-University of Berlin, D-13344
Berlin, Germany. daniel....@charite.de
Inflammatory bowel disease (IBD) results from a breakdown of tolerance
towards the indigenous flora in genetically susceptible hosts. Failure
of dendritic cells (DC) to interpret molecular microbial patterns
appropriately when directing innate and adaptive immune responses is
conceivable. Primary (conventional, non-monocyte generated) CD1c(+)
CD11c(+)CD14(-)CD16(-)CD19(-) myeloid blood or mucosal dendritic cells
(mDC) from 76 patients with Crohn's disease (CD) or ulcerative colitis
(UC) in remission, during flare-ups (FU) and 76 healthy or non-IBD
controls were analysed by fluorescence activated cell sorter (FACS)
flow cytometry and real-time polymerase chain reaction. Cytokine
secretion of freshly isolated, cultured and lipopolysaccharide (LPS)-
stimulated highly purified mDC (purity >95%) was assessed using
cytometric bead arrays (CBA). More cultured and stimulated circulating
mDC express CD40 in IBD patients. Stimulated circulating mDC from IBD
patients secrete significantly more tumour necrosis factor (TNF)-alpha
and interleukin (IL)-8. Toll-like receptor (TLR)-4 expression by mDC
was higher in remission and increased significantly in flaring UC and
CD patients compared with remission (P < 0.05) and controls (P <
0.001). Fluorochrome-labelled LPS uptake by mDC was evaluated at
different time-points over 24 h by measuring mean fluorescence
intensity (MFI). Circulating mDC from IBD patients take up more LPS
and the uptake begins earlier compared with controls (P < 0.05 in CD-
FU and UC-FU at 24 h). The frequency of mucosal mDC (P < 0.05) and the
number of CD40 expressing mucosal mDC is significantly greater in UC
and CD compared with non-IBD controls (P < 0.001 versus P < 0.01,
respectively). Our data suggest an aberrant LPS response of mDC in IBD
patients, resulting in an inflammatory phenotype and possibly
intestinal homing in acute flares.
PMID: 19664152 [PubMed - indexed for MEDLINE]
------
www.ncbi.nlm.nih.gov/pubmed/12730867
Impaired expression of peroxisome proliferator-activated receptor
gamma in ulcerative colitis.
Dubuquoy L, Jansson EA, Deeb S, Rakotobe S, Karoui M, Colombel JF,
Auwerx J, Pettersson S, Desreumaux P.
Equipe Propre INSERM 0114 sur la Physiopathologie des Maladies
Inflammatoires Intestinales, Lille, France.
Comment in:
Gastroenterology. 2003 May;124(5):1538-42.
BACKGROUND & AIMS: The peroxisome proliferator-activated receptor
gamma (PPAR gamma) has been proposed as a key inhibitor of colitis
through attenuation of nuclear factor kappa B (NF-kappa B) activity.
In inflammatory bowel disease, activators of NF-kappa B, including the
bacterial receptor toll-like receptor (TLR)4, are elevated. We aimed
to determine the role of bacteria and their signaling effects on PPAR
gamma regulation during inflammatory bowel disease (IBD). METHODS:
TLR4-transfected Caco-2 cells, germ-free mice, and mice devoid of
functional TLR4 (Lps(d)/Lps(d) mice) were assessed for their
expression of PPAR gamma in colonic tissues in the presence or absence
of bacteria. This nuclear receptor expression and the polymorphisms of
gene also were assessed in patients with Crohn's disease (CD) and
ulcerative colitis (UC), 2 inflammatory bowel diseases resulting from
an abnormal immune response to bacterial antigens. RESULTS: TLR4-
transfected Caco-2 cells showed that the TLR4 signaling pathway
elevated PPAR gamma expression and a PPAR gamma-dependent reporter in
an I kappa kappa beta dependent fashion. Murine and human intestinal
flora induced PPAR gamma expression in colonic epithelial cells of
control mice. PPAR gamma expression was significantly higher in the
colon of control compared with Lps(d)/Lps(d) mice. Although PPAR gamma
levels appeared normal in patients with CD and controls, UC patients
displayed a reduced expression of PPAR gamma confined to colonic
epithelial cells, without any mutation in the PPAR gamma gene.
CONCLUSIONS: These data showed that the commensal intestinal flora
affects the expression of PPAR gamma and that PPAR gamma expression is
considerably impaired in patients with UC.
PMID: 12730867
WOW this is a biggie. PPAR and LPS and crohn's all in a psor post....
thread..
randall... mostly ALL a huge RE-thread from one of FIVE Thousand LPS
posts. LOL