Tryptase as an inflammatory marker in allergic disease and asthma

Bachelet, Ido; Munitz, Ariel; Levi‐Schaffer, Francesca

doi:10.1586/1744666x.1.1.63

Cited by 14 publications

(9 citation statements)

References 102 publications

(75 reference statements)

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“…The best-characterized protease from this family is tryptase β, primarily because it was the first tryptase identified and it is the predominant protease and protein component of mast cells. Tryptase β has become a very useful diagnostic marker for the identification of mast cells and their activation 133, 134 . More importantly, tryptase β contributes to the pathogenesis of allergic inflammatory disorders, most notably asthma.…”

Section: Serine Proteasesmentioning

confidence: 99%

Extracellular Proteases as Targets for Drug Development

Čudić¹,

Fields²

2009

CPPS

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Proteases constitute one of the primary targets in drug discovery. In the present review, we focus on extracellular proteases (ECPs) because of their differential expression in many pathophysiological processes, including cancer, cardiovascular conditions, and inflammatory, pulmonary, and periodontal diseases. Many new ECP inhibitors are currently under clinical investigation and a significant increase in new therapies based on protease inhibition can be expected in the coming years. In addition to directly blocking the activity of a targeted protease, one can take advantage of differential expression in disease states to selectively deliver therapeutic or imaging agents. Recent studies in targeted drug development for the metalloproteases (matrix metalloproteinases, adamalysins, pappalysins, neprilysin, angiotensin-converting enzyme, metallocarboxypeptidases, and glutamate carboxypeptidase II), serine proteases (elastase, coagulation factors, tissue/urokinase plasminogen activator system, kallikreins, tryptase, dipeptidyl peptidase IV), cysteine proteases (cathepsin B), and renin system are discussed herein.

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Section: Serine Proteasesmentioning

confidence: 99%

Extracellular Proteases as Targets for Drug Development

Čudić¹,

Fields²

2009

CPPS

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“…Breathing difficulty manifests as wheezing manifests which can become life threatening in severe cases. While the causative allergens are not always identified, in allergic asthma degranulated MC are found in lung tissue and patient serum contains elevated antigen-specific IgE and tryptase levels 4 . Mast cells are thought to play an important role in pathogenesis as significant numbers are recruited to the airways and MC degranulation products are found in the broncholaveolar lavage fluid 5 .…”

Section: Introductionmentioning

confidence: 99%

Epoxyeicosatrienoic acids are involved in the C70 fullerene derivative–induced control of allergic asthma

Norton¹,

Wijesinghe²,

Dellinger³

et al. 2012

Journal of Allergy and Clinical Immunology

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Background Fullerenes are molecules being investigated for a wide range of therapeutic applications. We have shown previously that certain fullerene derivatives (FD) inhibit mast cell (MC) function in vitro, and here we examine their in vivo therapeutic effect on asthma, a disease in which MC play a predominant role. Objective To determine whether if an efficient MC-stabilizing FD (TGA) can inhibit asthma pathogenesis in vivo and to examine its in vivo mechanism of action. Methods Asthma was induced in mice and animals were treated intranasally (i.n.) with TGA either simultaneously with treatment or following induction of pathogenesis. Efficacy of TGA was determined through the measurement of airway inflammation, bronchoconstriction, serum IgE, bronchoalveolar lavage (BALF) cytokine and eicosanoid levels. Results We find that TGA treated mice have significantly reduced airway inflammation, eosinophilia, and bronchoconstriction. The TGA treatments are effective even when given after disease is established. Moreover, we report a novel inhibitory mechanism as TGA stimulate the production of an anti-inflammatory P-450 eicosanoid metabolites (epoxyeicosatrienoic acids; EET’s) in the lung. Inhibitors of these anti-inflammatory EET reversed TGA inhibition. In human lung MC incubated with TGA there was a significant upregulation of CYP1B gene expression while TGA also reduced IgE production from B cells. Lastly, MC incubated with EET and challenged through FcεRI had a significant blunting of mediator release compared to non-treated cells. Conclusion The inhibitory capabilities of TGA reported here suggest that FD may be used a platform for developing treatments for asthma.

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“…histamine and heparin proteoglycans) tryptase has become a diagnostic marker for the *Address correspondence to this author at the Abteilung Klinische Chemie und Klinische Biochemie, Klinikum der Ludwig-Maximilians-Universität, Nußbaumstr. 20, D-80336 München, Germany; Tel: 49-89-5160-5153; Fax: 49-89-5160-4735; E-mail: sommerhoff@med.uni-muenchen.de identification of mast cells and their activation (for reviews see [3,4]). Increased tryptase levels determined by immunoassay in the circulation primarily reflect mast cell degranulation, e.g.…”

Section: Introductionmentioning

confidence: 99%

Mast Cell Tryptase β as a Target in Allergic Inflammation: An Evolving Story

Sommerhoff¹,

Schaschke²

2007

CPD

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Tryptases comprise a group of trypsin-like serine proteases that are highly and selectively expressed in mast cells and to a lesser extent in basophils. Among them interest has been focused on tryptase beta, primarily because it was the first tryptase identified and because it is the predominant protease and protein component of mast cells. Subsequent studies have provided convincing evidence that tryptase beta is not only a clinically useful marker of mast cells and their activation but that it contributes to the pathogenesis of allergic inflammatory disorders, most notably asthma. The pathogenetic relevance together with the apparent lack of overt physiological functions has caused considerable interest in beta-tryptase as a potential therapeutic target. Meanwhile diverse tryptase inhibitors have been synthesized whose design in part was fostered by the structural analysis of the enzymatically active beta tryptase tetramer. Various compounds have been studied both in animal models and in man, providing proof of principle that tryptase inhibitors have therapeutic potential in asthma. Here we review the rationale to develop tryptase inhibitors and the approaches pursued, and also try to pinpoint some of the problems that hamper the development of clinically applicable drugs.

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Tryptase as an inflammatory marker in allergic disease and asthma

Cited by 14 publications

References 102 publications

Extracellular Proteases as Targets for Drug Development

Extracellular Proteases as Targets for Drug Development

Epoxyeicosatrienoic acids are involved in the C70 fullerene derivative–induced control of allergic asthma

Mast Cell Tryptase β as a Target in Allergic Inflammation: An Evolving Story

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Tryptase as an inflammatory marker in allergic disease and asthma

Cited by 14 publications

References 102 publications

Extracellular Proteases as Targets for Drug Development

Extracellular Proteases as Targets for Drug Development

Epoxyeicosatrienoic acids are involved in the C70 fullerene derivative–induced control of allergic asthma

Mast Cell Tryptase &#946; as a Target in Allergic Inflammation: An Evolving Story

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Mast Cell Tryptase β as a Target in Allergic Inflammation: An Evolving Story