Cutting Edge: AhR Is a Molecular Target of Calcitriol in Human T Cells.

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Cutting Edge: AhR Is a Molecular Target of Calcitriol in Human T Cells.

J Immunol. 2015 Aug 14;

Authors: Takami M, Fujimaki K, Nishimura MI, Iwashima M

Abstract
The immunoregulatory functions of vitamin D have been well documented in various immunological disorders, including multiple sclerosis, arthritis, and asthma. IL-10 is considered a chief effector molecule that promotes the vitamin D-induced immunosuppressive states of T cells and accessory cells. In this article, we demonstrate that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), has a profound inhibitory effect on the development of human Th9, a CD4 T cell subset that is highly associated with asthma, in an IL-10-independent manner. Our data show that calcitriol represses the expression of BATF, a transcription factor essential for Th9, via suppressing the expression of aryl hydrocarbon receptor, without an increase in IL-10. The data show a novel link between vitamin D and two key transcription factors involved in T cell differentiation.

PMID: 26276877 [PubMed – as supplied by publisher]

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Researchers uncover more detail of the molecular triggers behind asthma attacks – Imperial College London

Researchers uncover more detail of the molecular triggers behind asthma attacks
Imperial College London
A new study has tracked the molecular events that happen during asthma attacks to help explain how a common cold can trigger these attacks. Published in the American Journal of Respiratory and Critical Care Medicine, the research used novel sampling …

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Emerging Molecular Phenotypes of Asthma.

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Emerging Molecular Phenotypes of Asthma.

Am J Physiol Lung Cell Mol Physiol. 2014 Oct 17;

Authors: Ray A, Oriss TB, Wenzel SE

Abstract
Although asthma has long been considered a heterogeneous disease, attempts to define subgroups of asthma have been limited. In recent years both clinical and statistical approaches have been utilized to better merge clinical characteristics, biology and genetics. These combined characteristics have been used to define “phenotypes” of asthma, the observable characteristics of a patient determined by the interaction of genes and environment. Identification of consistent clinical phenotypes has been reported across studies. Now the addition of various ‘omics and identification of specific molecular pathways has moved the concept of clinical phenotypes towards the concept of molecular phenotypes. The importance of these molecular phenotypes is being confirmed through the integration of molecularly targeted biologic therapies. Thus, the term global asthma is poised to become obsolete, being replaced by terms which more specifically identify the pathology associated with the disease.

PMID: 25326577 [PubMed – as supplied by publisher]

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Molecular evolution of Peptide ligands with custom-tailored characteristics for targeting of glycostructures.

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Molecular evolution of Peptide ligands with custom-tailored characteristics for targeting of glycostructures.

PLoS Comput Biol. 2012 Dec;8(12):e1002800

Authors: Röckendorf N, Borschbach M, Frey A

Abstract
As an advanced approach to identify suitable targeting molecules required for various diagnostic and therapeutic interventions, we developed a procedure to devise peptides with customizable features by an iterative computer-assisted optimization strategy. An evolutionary algorithm was utilized to breed peptides in silico and the “fitness” of peptides was determined in an appropriate laboratory in vitro assay. The influence of different evolutional parameters and mechanisms such as mutation rate, crossover probability, gaussian variation and fitness value scaling on the course of this artificial evolutional process was investigated. As a proof of concept peptidic ligands for a model target molecule, the cell surface glycolipid ganglioside G(M1), were identified. Consensus sequences describing local fitness optima were reached from diverse sets of L- and proteolytically stable D lead peptides. Ten rounds of evolutional optimization encompassing a total of just 4400 peptides lead to an increase in affinity of the peptides towards fluorescently labeled ganglioside G(M1) by a factor of 100 for L- and 400 for D-peptides.

PMID: 23271960 [PubMed – in process]

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Researchers Find New Molecular Candidates For Treatment of Asthma and Allergies – Newswise (press release)

Researchers Find New Molecular Candidates For Treatment of Asthma and Allergies
Newswise (press release)
The research team, led by Toshiaki Kawakami, MD, Ph.D., is also the first to clarify the role of the HRF molecule in promoting asthma and some allergies, including identifying its receptor – a major finding that answers a long-held and important

and more »

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La Jolla Institute finds new molecular candidates for treatment of asthma and … – EurekAlert (press release)

La Jolla Institute finds new molecular candidates for treatment of asthma and
EurekAlert (press release)
SAN DIEGO – (December 1, 2011) La Jolla Institute for Allergy & Immunology scientists have identified the histamine releasing factor (HRF) molecule as a promising target for developing new treatments for a number of allergic reactions including asthma.

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Molecular Pathway, Asthma Inflammation and Future Treatment Options

Researchers Identify Molecular Pathway that leads to Inflammation in Asthma

Researchers at the University of Pittsburgh School of Medicine have identified a molecular pathway that helps explain how an enzyme elevated in asthma patients can lead to increased mucus production and inflammation that is characteristic of the lung condition. Their findings, reported online in this week’s Proceedings of the National Academy of Sciences, reveal unique interactions between biological molecules that could be targeted to develop new asthma treatments.

An enzyme called epithelial 15-lipoxygenase 1 (15LO1) metabolizes fatty acids to produce an eicosanoid known as 15 hydroxyeicosaetetranoic acid (15 HETE) and is elevated in the cells that line the lungs of asthma patients, explained Sally E. Wenzel, M.D., professor of medicine, Pitt School of Medicine, and director of the Asthma Institute at UPMC and Pitt School of Medicine. Her team showed in 2009 that the enzyme plays a role in mucus production.

“In this project, we found out 15 HETE is conjugated to a common phospholipid,” she said. “That complex, called 15HETE-PE, and 15LO1 behave as signaling molecules that appear to have a powerful influence on airway inflammation.”

By examining lung cells obtained by bronchoscopy from 65 people with asthma, the researchers found that both 15LO1 and 15HETE-PE displace an inhibitory protein called PEBP1 from its bond with another protein called Raf-1, which when freed can lead to activation of extracellular signal-regulated kinase(ERK). Activated ERK is commonly observed in the epithelial, or lung lining, cells in asthma, but until now the reason for that was not understood.

“This is an important study as it directly explores the important role of 15-lipoxygenase 1 in the airway epithelial cells of patients with asthma, which immediately establishes the relevance to human disease,” said Mark T. Gladwin, M.D., chief, Division of Pulmonary, Allergy and Critical Care Medicine, UPSOM.

Other experiments showed that knocking down 15LO1 decreased the dissociation of Raf-1 from PEBP1, which in turn reduced ERK activation. The pathway ultimately influences the production of factors involved in inflammation and mucus production.

“These results show us on both a molecular and mechanistic level and as mirrored by fresh cells from the patients themselves that the epithelial cells of people with asthma are very different from those that don’t have it,” Dr. Wenzel said. “It also gives us a potential treatment strategy: If we can prevent Raf-1 displacement, we might have a way of stopping the downstream consequences that lead to asthma.”

Co-authors include Jinming Zhao, Ph.D., Silvana Balzar, M.D., Claudette M. St. Croix, Ph.D., and John B. Trudeau, B.S., of UPSOM and the Asthma Institute; and Valerie B. O’Donnell Ph.D., of Cardiff University, United Kingdom. The study was funded by the National Institutes of Health and the American Heart Association.

Contact: Anita Srikameswaran
SrikamAV@upmc.edu
412-578-9193
University of Pittsburgh Schools of the Health Sciences
Pitt team finds molecular pathway that leads to inflammation in asthma
75.26.195.212

Pitt team finds molecular pathway that leads to inflammation in asthma – EurekAlert (press release)

Pitt team finds molecular pathway that leads to inflammation in asthma
EurekAlert (press release)
8 – Researchers at the University of Pittsburgh School of Medicine have identified a molecular pathway that helps explain how an enzyme elevated in asthma patients can lead to increased mucus production and inflammation that is characteristic of the

View full post on asthma – Google News