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Research description

Leukotrienes and prostanoids as mast cell mediators and modulators of asthmatic airway obstruction.

The aim of this project is to increase the understanding of mechanisms behind the development of asthma and other inflammatory airway diseases. Acknowledged internationally, our research group has over the years gathered experience and knowledge in leukotrienes, prostanoids and other inflammatory mediators. We have shown earlier that leukotrienes, together with histamine, cause some of the cardinal symptoms of asthma. The mechanisms through which leukotrienes exert their cellular effects are presently not well understood. Like leukotrienes, prostanoids are derived from the poly-unsaturated, essential fatty acid, arachidonic acid. The mechanisms and the location of prostanoid generation and effects differ importantly from those of the leukotrienes. The prostanoid family contains members that mediate asthma augmentation and airway inflammation. On the other hand, relief of asthma symptoms by other members of the family has also been described. Again, understanding how prostanoids mediate their cellular effects, particularly in the lung is presently only sketchily understood, at best. The main drive of this project is to elucidate the beneficial and malign mechanisms by which leukotrienes and prostanoids exert their effects on the different cellular structures of the lung. As this is very much and experimental undertaking, our set up consists of a network of co-operating basic researchers and clinicians and aims to provide comprehensive answers using animal models and human tissues. Implicit in our research is the aim for new discoveries which can lead to improved diagnosis and treatment of all airway inflammatory diseases, including asthma.

Financing

  • Swedish Research Council
  • Swedish Heart-Lung Foundation

Co-workers

  • Yvonne Nygren, secreterary
  • Åke Ryrfelt, Adjunct Professor
  • Mikael Adner, Associated Professor
  • Maria Kumlin, Associated Professor
  • Anita Sydbom, Associated Professor
  • Roelinde Middelveld, Project leader, PhD
  • Katarina Stark, Postdoc
  • Cecilia Kemi, Postdoc
  • Maciek Kupczyk, Postdoc
  • Margareta Andersson, BMA
  • Ingrid Delin, BMA
  • Susanna Kumlien-Georén, BMA, PhD
  • Stina Gustavsson, assistant
  • Linda Swedin, PhD student
  • Jesper Säfholm, PhD student
  • Hero Nikdin, student

Five selected publications

Wenzel SE, Barnes PJ, Bleecker ER, Bousquet J, Busse W, Dahlen SE, Holgate ST, Meyers DA, Rabe KF, Antczak A, Baker J, Horvath I, Mark Z, Bernstein D, Kerwin E, Schlenker-Herceg R, Lo KH, Watt R, Barnathan ES, Chanez P.

A Randomized, Double-blind, Placebo-controlled Study of TNF-{alpha} Blockade in Severe Persistent Asthma.

Am J Respir Crit Care Med. 2009 Jan 8.

Link to the abstract in PubMed

 

Selg E, Låstbom L, Ryrfeldt A, Kumlin M, Dahlén SE.

Effects of selective and non-selective COX inhibitors on antigen-induced release of prostanoid mediators and bronchoconstriction in the isolated perfused and ventilated guinea pig lung.

Prostaglandins Leukot Essent Fatty Acids. 2008;78:89-97.

Link to the abstract in PubMed

 

Selg E, Buccellati C, Andersson M, Rovati GE, Ezinga M, Sala A, Larsson AK, Ambrosio M, Låstbom L, Capra V, Dahlén B, Ryrfeldt A, Folco GC, Dahlén SE.

Antagonism of thromboxane receptors by diclofenac and lumiracoxib.

Br J Pharmacol. 2007;152:1185-95.

Link to the abstract in PubMed

 

Gaber F, James A, Delin I, Wetterholm A, Sampson AP, Dahlén B, Dahlén SE, Kumlin M.

Assessment of in vivo 5-lipoxygenase activity by analysis of leukotriene B4 in saliva: effects of treatment with zileuton.

J Allergy Clin Immunol. 2007;119:1267-8.

Link to the abstract in PubMed

 

Ressmeyer AR, Larsson AK, Vollmer E, Dahlèn SE, Uhlig S, Martin C.

Characterisation of guinea pig precision-cut lung slices: comparison with human tissues.

Eur Respir J. 200;28:603-11.

Link to the abstract in PubMed

 

Links

GA2LEN (Global Allergy and Asthma European Network)
Center of Allergy Research, Karolinska Institutet

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