This month we introduce the EAACI Asthma Section.
Chairman: Sebastian Johnston
1: Hot Topics
Ion channels as important sensors in airway sensory neurons:
Bessac et al. have shown, that TRPA1, an ion channel of the TRP gene family, serves as a neuronal sensor for oxidants in the airways. Inactivation of TRKA1 has been shown to lead to a reduction of excitability in sensory airway nerves of rodents, which is believed to induce a reduction of airway hyperresponsiveness to chemical stimuli. A TRPA1 anatomization might therefore be a suitable future therapy for airway disease.
Source: Bret F. Bessac, Michael Sivula, Christian A. von Hehn, Jasmine Escalera, Lauren Cohn and Sven-Eric Jordt. TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest. 2008 May;118(5):1899-910. PMID: 18398506
News on the role of eosinophils in asthma:
Shen et al. indicated eosinophils to be an important factor in airway remodeling in rodents asthma models. They showed that blocking the peptidyl-prolyl ismerase (Pin1) in eosinophils leads to a reduction of the amount of eosinphils in the lung and a reduction of TGF-beta produced by eosinophils. As they suggest Eosinophils to be keyplayers in collagendeposition in particular and airway remodeling in general, blocking of Pin1 is recomended as an antifibrotic therapy, which could reduce long term sequela of allergic asthma.
Source: Shen ZJ, Esnault S, Rosenthal LA, Szakaly RJ, Sorkness RL, Westmark PR, Sandor M, Malter JS. Pin1 regulates TGF-beta1 production by activated human and murine eosinophils and contributes to allergic lung fibrosis. J Clin Invest. 2008 Feb;118(2):479-90. PMID: 18188456
a) Airway Smooth Muscle in Asthma and COPD: Biology and Pharmacology
Author: Kian Fan Chung
April 2008, Wiley-Blackwell
b) The Resolution of Inflammation (Progress in Inflammation Research)
Authors: Adriano G. Rossi, Deborah A. Sawatzky
January 2008, Birkhäuser Basel
c) Regulatory T Cells and Clinical Application
Author: Shuiping Jiang
October 2008, Springer
3: Current Projects
A multidisciplinary study to identify the genetic an environmental causes of asthma in the European community.
The GABRIEL project, funded by the European Union FP6, involves over 150 scientists from 14 European countries, using the latest research across a variety of disciplines, including genetics, epidemiology and immunology, to identify key factors in the development of asthma. Asthma is caused by a combination of genetic and environmental effects, and despite being rare a hundred years ago, it has become increasingly common in developed societies across the world. Scientists believe rural environments are strongly protective against the disease, and increasing urbanisation may be contributing to the rise in the numbers affected.
As well as looking at genetic and environmental interactions, GABRIEL will study the molecular basis for environmental factors which can increase the risk of industrial asthma. It will also identify the agents which protect strongly against asthma in rural and farming communities and use genetics, genomics and proteomics to discover novel genetic and microbial factors that cause or protect against asthma.
4: Upcoming Events
XIX World Congress of Asthma
Date: 05-09 November 2008
Place: Monte-Carlo, Monaco
or click on the website www.aim-internationalgroup.com/2008/wca
2008 Allergy School on Epidemiology of Allergy and Respiratory Diseases
25 - 28 November: London, UK
XXVIII EAACI Congress in Poland 2009
June 2009, Warsaw, Poland
8th Workshop "Animal Models of Asthma"
January 2009, Hannover, Germany
5: Must Read Papers
TRPA1 is a major oxidant sensor in murine airway sensory neurons
Bret F. Bessac, Michael Sivula, Christian A. von Hehn, Jasmine Escalera, Lauren Cohn and Sven-Eric Jordt
J Clin Invest. 2008 May;118(5):1899-910.
Pin1 regulates TGF-beta1 production by activated human and murine eosinophils and contributes to allergic lung fibrosis.
Shen ZJ, Esnault S, Rosenthal LA, Szakaly RJ, Sorkness RL, Westmark PR, Sandor M, Malter JS.
J Clin Invest. 2008 Feb;118(2):479-90.
Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function.
Ober C, Tan Z, Sun Y, Possick JD, Pan L, Nicolae R, Radford S, Parry RR, Heinzmann A, Deichmann KA, Lester LA, Gern JE, Lemanske RF Jr, Nicolae DL, Elias JA, Chupp GL.
N Engl J Med 2008 Apr 17 358 (16):1682-91
Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease.
Nakao I, Kanaji S, Ohta S, Matsushita H, Arima K, Yuyama N, Yamaya M, Nakayama K, Kubo H, Watanabe M, Sagara H, Sugiyama K, Tanaka H, Toda S, Hayashi H, Inoue H, Hoshino T, Shiraki A, Inoue M, Suzuki K, Aizawa H, Okinami S, Nagai H, Hasegawa M, Fukuda T, Green ED, Izuhara K.
J Immunol. 2008 May 1;180(9):6262-9.
Distinct roles for IL-13 and IL-4 via IL-13 receptor alpha1 and the type II IL-4 receptor in asthma pathogenesis.
Munitz A, Brandt EB, Mingler M, Finkelman FD, Rothenberg ME.
Proc Natl Acad Sci U S A. 2008 May 20;105(20):7240-5. Epub 2008 May 14.
Resolvin E1 regulates interleukin 23, interferon-gamma and lipoxin A(4) to promote the resolution of allergic airway inflammation.
Haworth O, Cernadas M, Yang R, Serhan CN, Levy BD.
Nat Immunol. 2008 Aug;9(8):873-9. Epub 2008 Jun 22
NFAT1 Transcription Factor Regulates Pulmonary Allergic Inflammation and Airway Responsiveness
Fonseca BP, Olsen PC, Coelho LP, Ferreira TP, Souza HS, Martins MA, Viola JP.
Am J Respir Cell Mol Biol. 2008 Jul 29. [Epub ahead of print]
Steroid-Resistant Neutrophilic Inflammation in a Mouse Model of an Acute Exacerbation of Asthma
Ito K, Herbert C, Siegle JS, Vuppusetty C, Hansbro N, Thomas PS, Foster PS, Barnes PJ, Kumar RK.
Am J Respir Cell Mol Biol. 2008 May 12. [Epub ahead of print]
Arginase Inhibition Protects Against Allergic Airway Obstruction, Hyperresponsiveness & Inflammation
Maarsingh H, Zuidhof AB, Bos IS, van Duin M, Boucher JL, Zaagsma J, Meurs H.
Am J Respir Crit Care Med. 2008 Sep 15;178(6):565-73. Epub 2008 Jun 26.
Angiopoietin-1 Protects against Airway Inflammation and Hyperreactivity in Asthma
Simoes DC, Vassilakopoulos T, Toumpanakis D, Petrochilou K, Roussos C, Papapetropoulos A.
Am J Respir Crit Care Med. 2008 Jun 15;177(12):1314-21. Epub 2008 Mar 20.
6: Interesting asthma research centers in Europe
National Heart and Lung Institute, London, UK
Southampton General Hospital, Division of Infection, Inflammation and Repair, Respiratory Group http://www.som.soton.ac.uk/research/iir/
Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland
Department of Respiratory Medicine, Leiden University Medical Center, Leiden, Netherlands
Department of Respiratory Medicine and Laboratory of Translational Research in Obstructive Pulmonary Diseases, Ghent University, Ghent, Belgium
Department of Internal Medicine/Respiratory Medicine and Allergology, Sahlgrenska Academy, Göteborg University, Sweden
A new Comprehensive Pneumology Center (CPC) will be opened in Munich, by the Helmholtzzentrum and the Technische Universität München
Fraunhofer Institute, Department of Immunology, Allergology and Airway Research, Hannover, Germany