SKIN - Thyroid (HPA-axis) & Nerves with PSOR Genes
randall
In my earlier post today, i said:
In pant a cide---> you decide... LOL
I crack me uP....... but i said diecide. <G>
Humorous segue over...
========================
OK, now that my skin is tingling from the guttural guffaws.
Whats the latest on skin and psor besides those ugly butt psor
plaques?
LOOKY..... skin and nerves...........>
http://www.rdmag.com/News/2009/12/Life-Science-Researchers-find-hidden-sensory-system-in-the-skin/
Researchers find hidden sensory system in the skin
The human sensory experience is far more complex and nuanced than
previously thought, according to a groundbreaking new study published
in the December 15 issue of the journal Pain. In the article,
researchers at Albany Medical College, the University of Liverpool and
Cambridge University report that the human body has an entirely unique
and separate sensory system aside from the nerves that give most of us
the ability to touch and feel. Surprisingly, this sensory network is
located throughout our blood vessels and sweat glands, and is for most
people, largely imperceptible.
"It's almost like hearing the subtle sound of a single instrument in
the midst of a symphony," said senior author Frank Rice, PhD, a
Neuroscience Professor at Albany Medical College (AMC), who is a
leading authority on the nerve supply to the skin. "It is only when we
shift focus away from the nerve endings associated with normal skin
sensation that we can appreciate the sensation hidden in the
background."
The research team discovered this hidden sensory system by studying
two unique patients who were diagnosed with a previously unknown
abnormality by lead author David Bowsher, M.D., Honorary Senior
Research Fellow at the University of Liverpool's Pain Research
Institute. These patients had an extremely rare condition called
congenital insensitivity to pain, meaning that they were born with
very little ability to feel pain. Other rare individuals with this
condition have excessively dry skin, often mutilate themselves
accidentally and usually have severe mental handicaps. "Although they
had a few accidents over their lifetimes, what made these two patients
unique was that they led normal lives. Excessive sweating brought them
to the clinic, where we discovered their severe lack of pain
sensation," said Dr. Bowsher. "Curiously, our conventional tests with
sensitive instruments revealed that all their skin sensation was
severely impaired, including their response to different temperatures
and mechanical contact. But, for all intents and purposes, they had
adequate sensation for daily living and could tell what is warm and
cold, what is touching them, and what is rough and smooth."
The mystery deepened when Dr. Bowsher sent skin biopsies across the
ocean to Dr. Rice's laboratory, which focuses on multi-molecular
microscopic analyses of nerve endings in the skin, especially in
relation to chronic pain conditions such as those caused by nerve
injuries, diabetes, and shingles. These unique analyses were pioneered
by Dr. Rice at Albany Medical College (AMC) along with collaborators
at the Karolinska Institute in Stockholm, Sweden. "Under normal
conditions, the skin contains many different types of nerve endings
that distinguish between different temperatures, different types of
mechanical contact such as vibrations from a cell phone and movement
of hairs, and, importantly, painful stimuli," said Dr. Rice. "Much to
our surprise, the skin we received from England lacked all the nerve
endings that we normally associated with skin sensation. So how were
these individuals feeling anything?"
The answer appeared to be in the presence of sensory nerve endings on
the small blood vessels and sweat glands embedded in the skin. "For
many years, my colleagues and I have detected different types of nerve
endings on tiny blood vessels and sweat glands, which we assumed were
simply regulating blood flow and sweating. We didn't think they could
contribute to conscious sensation. However, while all the other
sensory endings were missing in this unusual skin, the blood vessels
and sweat glands still had the normal types of nerve endings.
Apparently, these unique individuals are able to 'feel things' through
these remaining nerve endings," said Dr. Rice. "What we learned from
these unusual individuals is that there's another level of sensory
feedback that can give us conscious tactile information. Problems with
these nerve endings may contribute to mysterious pain conditions such
as migraine headaches and fibromyalgia, the sources of which are still
unknown, making them very difficult to treat."
In addition to international collaborations such as this one, Dr. Rice
and his principle AMC colleague, Dr. Philip Albrecht, in the Center
for Neuropharmacology and Neuroscience, collaborate extensively with
neurologists Dr. Charles Argoff at AMC and Dr. James Wymer of Upstate
Clinical Research Associates, who also holds a joint AMC appointment.
All are co-authors on the study, which included normal subjects from
the Albany, N.Y. area. Several studies on chronic pain are being
conducted by this team with support from National Institutes of Heath
(NIH) and several pharmaceutical companies.
About Integrated Tissue Dynamics (INTIDYN)
To facilitate these collaborations, Dr. Rice and Dr. Albrecht,
recently founded a new biotechnology company, Integrated Tissue
Dynamics, LLC, also known as Intidyn (www.Intidyn.com).
<sniP>
===============
These Intidyn guys should hook up with psor realities.
AS in, what ties us to OUR PSOR plaques is coming in to focus.
Vegf is in the skin....
http://en.wikipedia.org/wiki/VEGF
www.ncbi.nlm.nih.gov/pubmed/19995970
2009 Dec 7.
Systemic anti-VEGF treatment strongly reduces skin inflammation in a
mouse model of psoriasis.
Schonthaler HB, Huggenberger R, Wculek SK, Detmar M, Wagner EF.
Banco Bilbao Vizcaya Argentaria (BBVA)-Foundation, Cancer Cell Biology
Programme, Centro Nacional de Investigaciones Oncológicas (CNIO),
28029 Madrid, Spain.
Although, vascular remodeling is a hallmark of many chronic
inflammatory disorders such as rheumatoid arthritis, inflammatory
bowel disease, and psoriasis, anti-vascular strategies to treat these
conditions have received little attention to date. We investigated the
anti-inflammatory activity of systemic blockade of VEGF-A by the
inhibitory monoclonal antibody G6-31, employing a therapeutic trial in
a mouse model of psoriasis. Simultaneous deletion of JunB and c-Jun
(DKO*) in the epidermis of adult mice leads to a psoriasis-like
phenotype with hyper- and parakeratosis and increased subepidermal
vascularization. Moreover, an inflammatory infiltrate and elevated
levels of cytokines/chemokines including TNFalpha, IL-1alpha/beta,
IL-6, and the innate immune mediators IL-22, IL-23, IL-23R, and
IL-12p40 are detected. Here we show that anti-VEGF antibody treatment
of mice already displaying disease symptoms resulted in an overall
improvement of the psoriatic lesions leading to a reduction in the
number of blood vessels and a significant decrease in the size of
dermal blood and lymphatic vessels. Importantly, anti-VEGF-treated
mice showed a pronounced reduction of inflammatory cells within the
dermis and a normalization of epidermal differentiation. These results
demonstrate that systemic blockade of VEGF by an inhibitory antibody
might be used to treat patients who have inflammatory skin disorders
such as psoriasis.
PMID: 19995970
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49 returns- keywords: vegf resveratrol -----> [pubmed]
Does resveratrol down regulate vegf naturally with genetics?
You tell me.. Or do it and then tell me. lol
Why don't we move directly in to the skin and look at pDC's?
OK
===========================
Hey LOOK, we've got a Krueger abstract today...
www.ncbi.nlm.nih.gov/pubmed/19996179
2009 Dec 8.
Human Langerhans cells induce distinct IL-22-producing CD4+ T cells
lacking IL-17 production.
Fujita H, Nograles KE, Kikuchi T, Gonzalez J, Carucci JA, Krueger JG.
Laboratory for Investigative Dermatology and Translational
Immunomonitoring Resource Center, The Rockefeller University, New
York, NY 10065.
IL-22 is a cytokine that acts mainly on epithelial cells. In the skin,
it mediates keratinocyte proliferation and epidermal hyperplasia and
is thought to play a central role in inflammatory diseases with marked
epidermal acanthosis, such as psoriasis. Although IL-22 was initially
considered a Th17 cytokine, increasing evidence suggests that T helper
cells can produce IL-22 even without IL-17 expression. In addition, we
have shown the existence of this unique IL-22-producing T cell in
normal skin and in the skin of psoriasis and atopic dermatitis
patients. In the present study, we investigated the ability of
cutaneous resident dendritic cells (DCs) to differentiate IL-22-
producing cells. Using FACS, we isolated Langerhans cells (LCs; HLA-DR
(+)CD207(+) cells) and dermal DCs (HLA-DR(hi)CD11c(+)BDCA-1(+) cells)
from normal human epidermis and dermis, respectively. Both LCs and
dermal DCs significantly induced IL-22-producing CD4(+) and CD8(+) T
cells from peripheral blood T cells and naive CD4(+) T cells in mixed
leukocyte reactions. LCs were more powerful in the induction of IL-22-
producing cells than dermal DCs. Moreover, in vitro-generated LC-type
DCs induced IL-22-producing cells more efficiently than monocyte-
derived DCs. The induced IL-22 production was more correlated with IFN-
gamma than IL-17. Surprisingly, the majority of IL-22-producing cells
induced by LCs and dermal DCs lacked the expression of IL-17, IFN-
gamma, and IL-4. Thus, LCs and dermal DCs preferentially induced
helper T cells to produce only IL-22, possibly "Th22" cells. Our data
indicate that cutaneous DCs, especially LCs, may control the
generation of distinct IL-22 producing Th22 cells infiltrating into
the skin.
PMID: 19996179
---
Keyword: IL-22 316 hits pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=IL-22&log$=activity
--------
IL-22 AND Psoria*-- 53 hits on pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=psoria*+AND+IL-22&log$=activity
If you add VEGF to this search - 3 returns (only one with keyword:
anti-vegf)
---
http://en.wikipedia.org/wiki/Langerhans_cell
Langerhans cells are dendritic cells[2] in the epidermis,[3]
containing large granules called Birbeck granules. They are normally
present in lymph nodes and other organs, including the stratum
spinosum layer of the epidermis. They can be found elsewhere,
particularly in association with the condition histiocytosis.
Function
On infection of an area of skin, the local Langerhans cells will take
up and process microbial antigens to become fully-functional antigen-
presenting cells.
Generally, dendritic cells in tissue are active in the capture, uptake
and processing of antigens. Once dendritic cells arrive in secondary
lymphoid tissue, however, they lose these properties while gaining the
capacity to interact with naive T-cells.
Langerhans cells are derived from the cellular differentiation of
monocytes with the marker "Gr-1" (also known as "Ly-6G/Ly-6C"). The
differentiation requires stimulation by colony stimulating factor
(CSF)-1.[6] They are similar in morphology and function to
macrophages. [7]
Langerin is a protein found in Langerhans cells,[8] and other types of
dendritic cells
---
How do these cells become what they are?
====
Pic's are good... more please:
http://www.john-libbey-eurotext.fr/e-docs/00/04/30/BF/texte_alt_jleejd00376_gr1.jpg
Use this one instead, then picture is clearer:
http://www.jle.com/e-docs/00/04/30/BF/article.md?fichier=images.htm
Does there have to be a gut--> SKIN connection in every post? LOL
Mine do:
http://www.nature.com/icb/journal/v80/n5/fig_tab/icb200263f2.html#figure-title
from:
http://www.nature.com/icb/journal/v80/n5/full/icb200263a.html
The abstract and pmid for the above:
www.ncbi.nlm.nih.gov/pubmed/12225381
Good one and so are his next 86 studies: author: von andrian
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=von+andrian&log$=activity
-----------------------
21 returns: calcitonin psoria* AND cgrp [pubmed]
www.ncbi.nlm.nih.gov/pubmed/19651223
2009 Nov;33(11):1144-8. Epub 2009 Aug 3.
Calcitonin gene-related peptide increases proliferation of human HaCaT
keratinocytes by activation of MAP kinases.
Yu XJ, Li CY, Xu YH, Chen LM, Zhou CL.
Department of Dermatology, Qilu Hospital, University of Shandong,
Jinan 250012, China.
Psoriasis is a chronic disease characterized by keratinocyte
hyperproliferation and inflammation. It has been demonstrated that the
expression of calcitonin gene-related peptide (CGRP) is elevated in
psoriasis lesions and CGRP-containing neuropeptide nerve fibers are
denser in the psoriatic epidermis. CGRP has been previously described
to influence proliferation of several cell types, such as Schwann
cell, tracheal epithelial cells, and human gingival fibroblasts. In
the present study, we determined the effect of CGRP on HaCaT
keratinocyte proliferation and the role of mitogen-activated protein
kinases (MAPKs) in CGRP induced keratinocyte proliferation. Our data
indicate CGRP increased [(3)H]-thymidine incorporation and MTT
activity of HaCaT in a concentration-dependent manner. CGRP also
enhanced serum-induced HaCaT cell proliferation. HaCaT cells cultured
with CGRP had a significant increase in phosphorylated ERK1/2, p38 and
JNK, and CGRP induced DNA synthesis was inhibited by PD 98059 or SB
203580, selective inhibitors of MAP kinase kinase (MEK, which is
upstream from ERK) and p38, respectively. These findings suggest that
HaCaT cell proliferate in response to CGRP, which is mediated by
phosphorylation of ERK1/2 and p38 MAPK.
PMID: 19651223
-----------
Back to aug 2000---
www.ncbi.nlm.nih.gov/pubmed/11776062
2000 Aug;113(8):747-51.
Calcitonin gene-related peptide in Langerhans cells in psoriatic
plaque lesions.
He Y, Ding G, Wang X, Zhu T, Fan S.
Department of Dermatology, People's Hospital, Beijing Medical
University, Beijing 100044, China.
OBJECTIVE: To study the mechanism of stress exacerbating psoriasis and
the involvement effect of neuropeptides in psoriatic pathogenesis, we
investigated the expression and secretion of calcitonin gene-related
peptide (CGRP) in psoriatic lesions, then identified the target cells
of CGRP, the characters of CGRP positive dendrite cells and the source
of CGRP in psoriatic plaque lesions. METHODS: Specific
radioimmunoassay (RIA) and immunohistochemistry staining methods were
used to determine CGRP secretive content and the target cells of CGRP
in psoriatic plaque lesion tissue of vulgaris psoriasis. Double
immunofluorenscence staining was done on psoriatic plaque lesion
sections by first using rabbit anti-human CGRP antibody and mouse anti-
human CD1a antibody, second using PE-conjugated anti-mouse
immunoglobulin and FITC-conjugated anti-rabbit immunoglobulin.
Confocal laser microscope showed the psoriatic lesion sections. Then
both digoxigenin labelled anti-sense and sense RNA probe of CGRP were
synthesized to make sure the source of CGRP on the dendrite cells. The
psoriatic lesion sections were studied by in situ hybridization.
RESULTS: The content of CGRP in vulgaris psoriatic plaque lesions was
higher than that of normal controls (P < 0.01). CGRP was also found on
the dermal microvascular endothelial cells and the epidermal dendrite
cells in psoriatic plague lesions. Further study showed that CGRP
existed on the surface of epidermal CD1a + Langerhans cell in
psoriatic plaque lesion. The CGRP mRNA expressed around the nucleus of
the Langerhans cells in psoriatic lesion. CONCLUSIONS: The
pathogenesis of psoriatic plaque lesions was closely related to the
overexpression of neuropeptide CGRP. The CGRP contacted with the
dermal microvascular endothelial cells and epidermal dendrite cells in
psoriatic plaque lesion. The CGRP positive epidermal dendrite cell was
CD1a + Langerhans cell. The Langerhans cell itself expressed CGRP
mRNA.
PMID: 11776062
=========================
SO Susan is once again, RIGHT on.
http://en.wikipedia.org/wiki/Calcitonin
Calcitonin is a 32-amino acid linear polypeptide hormone that is
produced in humans primarily by the parafollicular cells (also known
as C-cells) of the thyroid, and in many other animals in the
ultimobranchial body.[2] It acts to reduce blood calcium (Ca2+),
opposing the effects of parathyroid hormone (PTH).[3] It has been
found in fish, reptiles, birds, and mammals. Its importance in humans
has not been as well established as its importance in other animals,
as its function is usually not significant in the regulation of normal
calcium homeostasis.[4]
---------------------
So?
It's skin and thyroid and genetics LOL
randall...