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1 5th August 16:46
kofi
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Default Tight junction gaps implicated in eczema (eczema diabetes asthma epidermal pollen)


Cathelicidin is both an anti-inflammatory and a regulator of tight
junction gaps (via EGFR). It's defective in atopic dermatitis and may
be tied directly into the tight junction gap problem.

<http://www.sciencedaily.com/releases/2010/12/101217145920.htm>

Major Shift in Understanding How Eczema Develops

ScienceDaily (Dec. 18, 2010) ‹ Like a fence or barricade intended to
stop unwanted intruders, the skin serves as a barrier protecting the
body from the hundreds of allergens, irritants, pollutants and microbes
people come in contact with every day. In patients with eczema, or
atopic dermatitis, the most common inflammatory human skin disease, the
skin barrier is leaky, allowing intruders -- pollen, mold, pet dander,
dust mites and others -- to be sensed by the skin and subsequently wreak
havoc on the immune system.

While the upper-most layer of the skin -- the stratum corneum -- has
been pinned as the culprit in previous research, a new study published
in the Journal of Allergy and Clinical Immunology found that a second
skin barrier structure, consisting of cell-to-cell connections known as
tight junctions, is also faulty in eczema patients and likely plays a
role in the development of the disease. Tightening both leaky barriers
may be an effective treatment strategy for eczema patients, who often
have limited options to temper the disease.

"Over the past five years, disruption of the skin barrier has become a
central hypothesis to explain the development of eczema," said Lisa
Beck, M.D., lead study author and associate professor in the Department
of Dermatology at the University of Rochester Medical Center. "Our
findings challenge the belief that the top layer of the skin or stratum
corneum is the sole barrier structure: It suggests that both the stratum
corneum and tight junctions need to be defective to jumpstart the
disease."

Currently, there are no treatments that target skin barrier dysfunction
in eczema. To treat eczema, which causes dry, red, itchy skin,
physicians typically prescribe anti-inflammatory drugs, like prednisone,
and a variety of topical anti-inflammatory creams and ointments. But,
modest benefit, negative side effects and cost concerns associated with
these therapies leave patients and doctors eagerly awaiting new
alternatives.

"We want to figure out what current eczema therapies do to both barrier
structures and start thinking about new treatments to close the breaks
that let irritants in and water out and subsequently drive the
inflammation and dryness that is characteristic of the disease," noted
Beck, who treats eczema patients in addition to conducting research on
the condition.

To better understand the role of tight junctions in eczema, Beck and her
team studied skin samples from eczema patients and healthy individuals.
Using resistance and permeability tests, they discovered that tight
junctions, which act like a gate controlling the passage of water and
particles, were strong and tight in healthy skin samples, yet loose and
porous in the skin of eczema patients.

On further investigation, they found that a particular tight junction
protein, claudin-1, which determines the strength and permeability of
tight junctions in skin, is significantly reduced in the skin of eczema
patients, but not in healthy individuals or individuals with psoriasis,
another common chronic skin disease. They demonstrated that reducing
claudin-1 expression in skin cells from healthy donors made the tight
junctions leaky and more permeable, a finding in line with results of
other research groups.

"Since claudin-1 was only reduced in eczema patients, and not the other
controls, it may prove to be a new susceptibility gene in this disease,"
said Anna De Benedetto, M.D., postdoctoral-fellow at the Medical Center
and first author of the new study. "Our hypothesis is that reduced
claudin-1 may enhance the reactivity to environmental antigens and lead
to greater allergen sensitization and susceptibility in people with
eczema."

If the team's hypothesis stands up in future research, increasing
claudin-1 to combat eczema could be a new treatment approach worth
exploring. The University of Rochester has applied for patent protection
for increasing claudin-1 with drug compounds to treat eczema.

Barrier problems, and in particular tight junction defects, are
recognized as a common feature in many other inflammatory diseases, such
as inflammatory bowel disease and asthma, where the lining of the
intestine and the airways is weakened, which is why Beck and her team
decided to focus on the role of this barrier structure in eczema.

Eczema affects up to 17 percent of children and about six percent of
adults in the United States -- close to 15 million Americans. While
there are varying severities of eczema, all have an itch that can make
it difficult to focus on daily activities and to sleep. People with
eczema are often counseled to minimize their exposure to allergens, but
that is a difficult task given the hundreds of allergens people are
exposed to each day.

Beck, who began the research while at Johns Hopkins University, plans to
build on these findings by investigating the immunologic consequences of
tight junction disruption in the skin and whether there is a
relationship between barrier disruption and subjects' intractable itch.
In addition, as part of a contract with the National Institute of
Allergy and Infectious Diseases (NIAID) at the National Institutes of
Health, called the Atopic Dermatitis Research Network, Beck, in
collaboration with Kathleen Barnes, Ph.D., at Johns Hopkins, will
perform gene mapping of claudin-1 to try to identify mutations in
patients with eczema.

The current research was funded by the Atopic Dermatitis and Vaccinia
Network at NIAID, the National Eczema Association and the Mary Beryl
Patch Turnbull Scholar Program. Along with Beck and De Benedetto, Andrei
I. Ivanov, Ph.D., Steve N. Georas, M.D., Kunzhong Zhang, Ph.D.,
Sadasivan Vidyasagar, M.D., Ph.D., and Takeshi Yoshida, Ph.D., from the
University of Rochester Medical Center participated in the research.
Scientists from Johns Hopkins University School of Medicine, National
Jewish Health, the University of California, San Diego, Children's
Hospital Boston, Oregon Health & Science University, the University of
Bonn (Germany), Technische Universität München (Germany) and Johns
Hopkins Bloomberg School of Public Health contributed as well.
------------------------------------------------------------------------
Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily
staff) from materials provided by University of Rochester Medical Center.

Invest Ophthalmol Vis Sci. 2010 Apr;51(4):1891-7. Epub 2009 Sep 24.
Related Citations, References for this PMC Article, Free in PMC, LinkOut
*
LL-37 via EGFR transactivation to promote high glucose-attenuated
epithelial wound healing in organ-cultured corneas.
Yin J, Yu FS.
Departments of Ophthalmology, Kresge Eye Institute, Wayne State
University School of Medicine, Detroit, Michigan, USA.

Purpose. Patients with diabetes are at higher risk for delayed corneal
reepithelialization and infection. Previous studies indicated that high
glucose (HG) impairs epidermal growth factor receptor (EGFR) signaling
and attenuates ex vivo corneal epithelial wound healing. The authors
investigated the effects of antimicrobial peptide LL-37 on HG-attenuated
corneal epithelial EGFR signaling and wound closure. Methods. Human
corneal epithelial cells (HCECs) were stimulated with LL-37.
Heparin-binding EGF-like growth factor (HB-EGF) shedding was assessed by
measuring the release of alkaline phosphatase (AP) in a stable HCEC line
expressing HB-EGF-AP. Activation of EGFR, phosphoinositide 3-kinase
(PI3K), and extracellular signal-regulated kinases 1/2 (ERK1/2) was
determined by Western blot ****ysis. Corneal epithelial wound closure
was assessed in cultured HCECs and porcine corneas. LL-37 expression was
determined by immune dot blot. Results. LL-37 induced HB-EGF-AP release
and EGFR activation in a dose-dependent manner. LL-37 prolonged EGFR
signaling in response to wounding. LL-37 enhanced the closure of a
scratch wound in cultured HCECs and partially rescued HG-attenuated
wound healing in an EGFR- and a PI3K-dependent manner and restored
HG-impaired EGFR signaling in cultured porcine corneas. HG attenuated
wounding-induced LL-37 expression in cultured HCECs. Conclusions. LL-37
is a tonic factor promoting EGFR signaling and enhancing epithelial
wound healing in normal and high glucose conditions. With both
antimicrobial and regenerative capabilities, LL-37 may be a potential
the****utic for diabetic keratopathy.

Publication Types:
* Research Support, N.I.H., Extramural
* Research Support, Non-U.S. Gov't

PMID: 19797203


1: Clin Rev Allergy Immunol. 2010 Dec 22; [Epub ahead of print]
Related Citations, LinkOut

Innate Immunity in Atopic Dermatitis.
Wollenberg A, Rawer HC, Schauber J.
Department of Dermatology and Allergy, Ludwig-Maximilian-University of
Munich, Frauenlobstr. 9-11, 80337, Munich, Germany,

Atopic dermatitis (AD) is a clinically defined, highly pruritic, chronic
inflammatory skin disease. In AD patients, the combination of a genetic
predisposition for skin barrier dysfunction and dysfunctional innate and
adaptive immune responses leads to a higher frequency of bacterial and
viral skin infections. The innate immune system quickly mobilizes an
unspecific, standardized first-line defense against different pathogens.
Defects in this system lead to barrier dysfunction which results in
increased protein allergen penetration through the epidermis and
predisposes to secondary skin infections. Two loss-of-function mutations
in the epidermal filaggrin gene are associated with AD. Also, inducible
endogenous antibiotics such as the antimicrobial peptides cathelicidin
and the beta-defensins may show defective function in lesional AD skin.
Eczema herpeti*** is a disseminated viral infection almost exclusively
diagnosed in AD patients, which is based on unmasking of the viral entry
receptor nectin-1, lack of cathelicidin production by keratinocytes, and
depletion of Type I IFN-producing plasmacytoid dendritic cells from AD
skin. Future the****utic approaches to AD may include enhancement of
impaired innate in addition to downregulation of dysfunctional adaptive
immunity.

PMID: 21181301
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2 5th August 16:46
ernie
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Default Tight junction gaps implicated in eczema (eczema)


I'll let hunky farrel into my tight junction gap. Ernie
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3 5th August 16:46
ernie
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Default Tight junction gaps implicated in eczema (eczema)


asshole farrel posts what the hunk of shit would like to do to herself
using my name due to her perversity. Ernie
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4 5th August 16:46
marcus
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Why would he do that? Marcus
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5 5th August 16:46
ernie
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Default Tight junction gaps implicated in eczema (eczema)


On Jan 3, 5:04 pm, Ernie <eprimea...@gmail.com> wrote:


He wouldn't, I'm just not going to let him get away without a retort. Ernie
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6 5th August 16:46
ernie
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Because she is perverted. Ernie
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7 5th August 16:46
ernie
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asshole farrel meant she. Ernie
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8 8th August 03:59
ernie
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Default Tight junction gaps implicated in eczema (eczema)


asshole farrel babbles using my name. Ernie
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