Tag: Tolllike

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BCM Researcher Suggests: The pathway to asthma winds through Toll-like … – BioNews Texas


BioNews Texas

BCM Researcher Suggests: The pathway to asthma winds through Toll-like …
BioNews Texas
Early studies carried out where mice were given a cocktail of proteinases demonstrated that these enzymes induced an allergic disease response, similar to asthma. Studying the role of proteinases in allergy, Dr. Corry demonstrated that these …

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Pathway to asthma winds through Toll-like receptor 4 – BCM News


Medical Xpress

Pathway to asthma winds through Toll-like receptor 4
BCM News
Asthma is part of a battle that takes place as the immune system marshals its forces to fight off an invading organism-or what mimics such invaders. The ensuing fight takes a significant toll on the human airway and lungs, often generating a violent …
Clues emerge to explain allergic asthmaScience News
Insights into Asthma, And Maybe the Hygiene HypothesisBioWorld Online

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Penehyclidine hydrochloride: a potential drug for treating COPD by attenuating Toll-like receptors.

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Penehyclidine hydrochloride: a potential drug for treating COPD by attenuating Toll-like receptors.

Drug Des Devel Ther. 2012;6:317-22

Authors: Xiao HT, Liao Z, Tong RS

Abstract
BACKGROUND: The aim of this review was to evaluate and summarize the available scientific information on penehyclidine hydrochloride (PHC) for the treatment of chronic obstructive pulmonary disease (COPD) as a result of its ability to attenuate Toll-like receptors. Penehyclidine hydrochloride is an anticholinergic drug manufactured in China, with both antimuscarinic and antinicotinic activity. PHC is used widely in the clinic as a reversal agent in cases of organic phosphorus poisoning and soman poisoning, but also may also have an important role as a bronchodilator in the treatment of obstructive airway disease, including asthma and, in particular, COPD.
METHODS: Our bibliographic sources included the CAPLUS, MEDLINE, REGISTRY, CASREACT, CHEMLIST, CHEMCATS, and CNKI databases, updated to September 2012. In order to assess the data in detail, we used the search terms “penehyclidine hydrochloride,” “COPD,” “muscarinic receptor,” and “toll-like receptors.” Papers were restricted to those published in the English and Chinese languages, and to “paper” and “review” as the document type. Patents were also reviewed.
RESULTS: Our survey mainly yielded the results of research on PHC and the mechanisms of COPD. COPD is a preventable and treatable disease with some significant extrapulmonary manifestations that may contribute to its severity in some patients. Recently, it has been shown that muscarinic receptors may interact with Toll-like receptors. Basic and clinical studies of the relationship between the mechanism of action and the effects of PHC in the respiratory tract have been studied by a number of laboratories and institutions. The main advantages of PHC are that it has few M(2) receptor-associated cardiovascular side effects and attenuates Toll-like receptors.
CONCLUSION: PHC may be a promising candidate agent in the treatment of COPD in the future because of its ability to attenuate Toll-like receptors. This review should be of help to those intending to research this topic further.

PMID: 23139625 [PubMed – in process]

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Flagellin Induces the Expression of Thymic Stromal Lymphopoietin in Human Keratinocytes via Toll-Like Receptor 5.

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Flagellin Induces the Expression of Thymic Stromal Lymphopoietin in Human Keratinocytes via Toll-Like Receptor 5.

Int Arch Allergy Immunol. 2010 Nov 25;155(1):31-37

Authors: Le TA, Takai T, Vu AT, Kinoshita H, Chen X, Ikeda S, Ogawa H, Okumura K

Background: Thymic stromal lymphopoietin (TSLP), highly expressed by keratinocytes in skin lesions of atopic dermatitis patients and bronchial epithelial cells in asthma, plays a key role in allergic diseases. Information on triggers for the release of TSLP in keratinocytes is still limited. Keratinocytes express Toll-like receptor (TLR) 5, the ligand for which is flagellin, the major structural protein of the flagella of Gram-negative bacteria. IL-4, IL-13 and TNF-? (Th2/TNF) are associated with allergic diseases. TGF-?, one of the ligands for the epidermal growth factor receptor, is overexpressed in keratinocytes in atopic dermatitis. We investigated the induction of TSLP expression in keratinocytes stimulated with flagellin and its modulation by the Th2/TNF cytokines and TGF-?. Methods: Primary human keratinocytes were stimulated with flagellin with or without cytokines. The TSLP released was measured by ELISA. Gene expression was analyzed by quantitative real-time PCR. Results: Stimulation of keratinocytes with flagellin induced the release of TSLP protein and upregulation of the gene expression of TSLP and other pro-inflammatory molecules. The flagellin-induced release of TSLP was enhanced by the Th2/TNF cytokines or TGF-?. Small interfering RNA-mediated knockdown of TLR5 expression suppressed the flagellin-induced TSLP gene expression. Conclusions: Flagellin induces TSLP expression in keratinocytes via TLR5 and the expression can be upregulated by a cytokine milieu with Th2/TNF or TGF-?, suggesting that exposure of barrier-defective skin to Gram-negative bacteria or environmental flagellin contributes to the initiation and/or amplification of Th2-type skin inflammation including atopic dermatitis through the induction of TSLP expression in keratinocytes.

PMID: 21109746 [PubMed – as supplied by publisher]

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