Gallo & LTA -- CXC Receptors -- Alcohol Cure? - Th22 - GERD - B Cells
randall
http://www.newscientist.com/article/dn18184-friendly-bacteria-keep-your-skins-defences-in-check.html
Friendly bacteria keep your skin's defences in check
12:20 23 November 2009
by Linda Geddes
Being caked in germs sounds unpleasant, but "friendly" bacteria living
on our skin may have the vital role of keeping in check inflammation
triggered by injury and unwanted bacteria.
The discovery extends the list of bacteria that the human body relies
on to function. It also suggests that antibacterial hand gels and
soaps might exacerbate skin conditions characterised by excessive
inflammation.
The most common family of bacteria found on the skin is
Staphylococcus, the member of which are harmless, unless they get into
wounds. To see if they might actually be useful to humans, ____Richard
Gallo____ at the University of California, San Diego, and his
colleagues added molecules released by Staphylococcus to cells found
in human skin.
They found that one molecule, called lipoteichoic acid (LTA), stopped
some skin cells from releasing chemicals that trigger inflammation,
part of the body's immune response. LTA had a similar effect when
added to the skin of live mice.
Gut protection
Gallo says that although inflammation is essential for recovery from
injury, the ability to damp it down is key because prolonged
inflammation can lead to skin diseases like psoriasis.
His team also notes that LTA's protective role seems limited to the
skin's surface: in immune cells taken from deeper layers, it provoked
inflammation.
Skin Staphylococci aren't the only bacteria we rely on. In the gut,
friendly bacteria control inflammation, while in the mouth they may
kill strains that cause decay and halitosis
Gallo speculates that bacteria may be also help regulate inflammation
in other areas of the body such as the lining of the lungs and nose,
although different species of friendly bacteria may be responsible.
Excessive antimicrobials
As for what the Staphylococci get out of this relationship, Gallo says
that many of them are resistant to antimicrobial compounds released by
human skin that kill off other microbes. "One of the things they are
getting out of it is a protective niche with nutrients," he says.
Gallo also cautions against the over-use of antibacterial gels and
soaps. Although these might be helpful in curbing transmission of
swine flu, excessive or long-term use might also have some negative
consequences.
"Any scratch that you might encounter is going to initiate
inflammation and the presence of these microbes will help modulate
that inflammatory response," says Gallo. "If you do not allow those
normal microbes to survive then you lose this ability. That could be
something that occurs with excessive use of indiscriminate
sterilisers."
Journal reference: Nature Medicine, DOI: 10.1038/nm.2062
----
Richard Gallo has been spot on with LL-37, TLR's LPS etc: [145
studies]
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Gallo%20RL%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract
I hadn't seen this one before:
www.ncbi.nlm.nih.gov/pubmed/19781786
Engagement of CD44 by hyaluronan suppresses TLR4 signaling and the
septic response to LPS.
Muto J, Yamasaki K, Taylor KR, Gallo RL.
Division of Dermatology, University of California, San Diego and VA
San Diego Health Care System, San Diego, CA 92161, USA.
Fragments of hyaluronan released after injury bind and activate TLR4
in a complex with CD44. Here we investigated if the recognition of
hyaluronan by CD44 and TLR4 alters lipopolysaccaride (LPS)
responsiveness and thus could alter the septic response. In contrast
to mice injected with LPS, mice exposed to hyaluronan prior to LPS had
greatly decreased serum IL-6 and TNFalpha and were protected from
symptoms of sepsis. The protective effect of HA was not seen in Cd44
(-/-) mice. Consistent with our findings in vivo, addition of
hyaluronan to macrophages before LPS exposure significantly decreased
the release of IL-6 and TNFalpha and this effect was not seen in
macrophages from Cd44(-/-) mice. Investigation of the mechanism
responsible for inhibition of LPS activation showed hyaluronan
treatment resulted in an increase in peritoneal macrophage A20 mRNA
expression, and that this was significantly reduced in macrophages
from Cd44(-/-) mice and Tlr4(-/-) mice. Suppression of the A20
response with siRNA inhibited the ability of hyaluronan to protect
against the cytokine response to LPS. Therefore, our results show that
hyaluronan acts through TLR4, CD44 and A20 to stimulate a unique
cellular response that can protect against the septic response to LPS.
PMID: 19781786
Raise your HA levels and lower your LPS and Th1 skew and psoriasis is
what i'm seeing.
Or i want to SEE. LOL
And since I did trials with HA it was in that experience as WELL
check the group: for me and HA. ;~/
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http://www.pipelinereview.com/index.php/2009112230958/Background-briefs/CXC-Receptors-and-their-Ligands-targets-for-inflammation-and-cancer.html
CXC Receptors and their Ligands: targets for inflammation and cancer
22 Nov 2009
Chemokines, or chemotactic cytokines, and their receptors have been
discovered as essential and selective mediators in leukocyte migration
to inflammatory sites and to secondary lymphoid organs. Besides their
functions in the immune system, they also play a critical role in
tumor initiation, promotion and progression. There are four subgroups
of chemokines. The CXC or alpha subgroup is one of the four and can be
further subdivided in the ELR(+) and ELR(-) chemokines. Members that
contain the ELR motif bind to CXC chemokine receptor 2 (CXCR2) and are
angiogenic. In contrast, most of the CXC chemokines without ELR motif
bind to CXCR3 and are angiostatic. An exception is the angiogenic ELR
(-)CXC chemokine stromal cell-derived factor-1 (CXCL12/SDF-1), which
binds to CXCR4 and CXCR7 and is implicated in tumor metastasis.
The CXC receptors and their ligands are promising targets for drug
development. The first approved and marketed drug is plerixafor
(AMD3100), a small molecule inhibitor of the CXCR-4/SDF-1 axis, used
for stem cell mobilization. CXCR1 and CXC chemokine receptor 2 (CXCR2)
are believed to be crucially involved in the direct migration and
activation of leukocytes. Their ligands are supposed to play a key
role in several inflammatory diseases and this makes them and their
receptors attractive therapeutic targets for inflammatory diseases
such as COPD, asthma, psoriasis, ulcerative colitis and rheumatoid
arthritis.
==============
Quit drinking alcohol?
For psoriatics? What could be better?
http://www.jpost.com/servlet/Satellite?cid=1258705155872&pagename=JPost%2FJPArticle%2FShowFull
Nov 22, 2009 7:23
Health Scan: New slow-release pill effective for drinkers
By JUDY SIEGEL-ITZKOVICH
Just in time for the government's new effort to fight alcoholism,
especially among young people, Hadassah University Medical Center
researchers have found that taking a new slowrelease pill before
having a drink can lower the level of alcohol in the blood,
dramatically improve motor and cognitive functions and decrease
alcohol cravings.
Metadoxine, a drug currently used to treat alcoholism, is ordinarily
effective for less than an hour. But a slow-release formula developed
by an Israeli start-up company named Alcobra Ltd. vastly extends the
effects. Although those tested on Metadoxine were included in only a
Phase-I clinical trial on healthy people, the effects are very
significant.
The clinical trials were conducted by researchers from Hadassah's
liver unit, psychiatry department and internal medicine unit. Internal
medicine specialists Dr. Meir Mizrahi and Dr. Gadi Lalazar, who headed
the team, presented their findings Sunday at the annual conference of
the American Association for the Study of Liver Diseases (AASLD) in
Boston. More than 7,000 researchers from 55 countries, including eight
Israelis from Hadassah, attended.
After a 10-hour fast, the six participants in the first phase of the
clinical trial took one dose of the slow-release Metadoxine formula
(1,190 to 2,100 ml.) and then drank 70 ml. of alcohol. During the 12-
hour observation period, blood was drawn for alcohol and Metadoxine
levels, and the subjects were graded on a driving simulator and a
continuous performance test used to diagnose attention-deficit,
hyperactivity disorder, memory and cognitive skills. They also
answered a questionnaire about their level of craving for alcohol.
All of participants had a decreased blood level of alcohol and the
results of their motor and cognitive tests were positive; none
developed any related side effects, the researchers said. They believe
that slow-release Metadoxine can help in the treatment of alcoholism
and its side effects, and are planning to enlarge the scope of their
study in the coming months.
The Hadassah-Alcobra project is being conducted under the auspices of
Hadasit, Hadassah's technology transfer company.
A methacetin breath test (MBT) that can be performed quickly and
noninvasively has been proven to accurately predict survival in
patients with viral hepatitis, and may be used as an adjunctive tool
to MELD (Model for End-Stage Liver Disease). It serves as a scoring
system adopted by the United Network for Organ Sharing to assess liver
disease severity and determine threemonth mortality. Viral hepatitis
progresses at an unpredictable rate, and the addition of another way
of assessing progression can serve as an important adjunct to MELD.
Researchers in the Liver Unit at Hadassah Medical Center in Jerusalem
studied 395 patients with viral hepatitis. The MBT accurately
predicted survival. Of those patients, 11 had died in the two years in
which data were collected. MBT identified 9 of these 11 as being high-
risk. Whereas six of those 11 deaths occurred in patients with a MELD
score less than 15 - patients considered at low risk by the MELD
scoring system. In addition, MBT accurately predicted survival in
patients with a higher MELD score and, therefore, at increased risk as
defined by MELD.
PSORIASIS CLARIFICATION Last week's Health Scan item on a small
protein named IGFBP7 whose lack causes rapid division of skin cells
being "discovered" by dermatologists at Tel Aviv Sourasky Medical
Center was incorrect and based on information provided by Sourasky. In
fact, the protein's significance related to psoriasis was discovered
three years ago by Dr. Malka Hochberg and colleagues at Hadassah
University Medical Center in Jerusalem's Ein Kerem. The Sourasky team
based its findings on the Hadassah discovery.
============
This is a re-post:
Th22 is so BIG i've elected to run it again.
32 hits (right now) on google news in Major Languages:
http://news.google.com/news/search?aq=f&um=1&cf=all&ned=us&hl=en&q=Th22
http://www.eurobiotechnews.eu/service/start-page/top-news/?no_cache=1&tx_ttnews%5Btt_news%5D=11656&tx_ttnews%5BbackPid%5D=12&cHash=bf4cfe1667
German researchers identify immune cells that trigger psoriasis
22.11.09 Munich – German researchers have discovered a novel type of
immune cell in the skin of individuals with chronic skin inflammations
which could lead to long-lasting therapies against asthma, COPD,
psoriasis, as well as assist healing (J. Clin. Invest. (doi:10.1172/
JCI40202). The so-called Th22 cells boosted inflammation, against
invading bacteria or viruses, when the immune messengers
interleukin-22 (IL-22) and the proinflammatory cytokine tumor necrosis
factor alpha (TNF alpha) were expressed. However, in the absence of
TNF, they calmed inflammatory processes, and improved wound healing
and tissue repair. This mode of action is in line with the previous
discovery that IL-22 triggers psoriasis in mice in a dose-dependent
manner, and that inhibition of the cytokine improves psoriasis
symptoms. To date, the researchers have found Th22 cells in the outer
skin layer (epidermis) of patients with atopic eczema, psoriasis, and
allergic skin diseases. They appear to be a part of the body’s first
line of defence against infections, dubbed the innate immune system.
In healthy skin, the cells contribute to immune protection and wound
healing. Now the researchers are seeking to crack the detailed
mechanisms by which the cells contribute to allergic diseases. Their
findings could help with the development of future therapies against
the serious disorders. The researchers from Italy, the UK and Germany
headed by Stefanie Eyerich from Helmholtz Centre Munich said the
discovery is a milestone on the path towards the development of new
treatment methods for psoriasis and allergic reactions, as well as
against asthma. Like other T helper cells, Th22 cells belong to a part
of the immune system that can recognise damaging pathogens even after
a longer period of time. This means that any treatment targeting these
cells would potentially have a long-term effect.
http://www.jci.org/articles/view/40202
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Is GERD an Autoimmune condition?
http://www.newswise.com/articles/view/558821/?sc=mwhr;xy=5049990
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B Cells and the road to cancer or autoimmune
http://insciences.org/article.php?article_id=7673
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randall.... back to Ha trials? maybe after L. Plantarum