Dr. C. Frieke Kuper
P.O. Box 360
3700 AJ Zeist
Tel: +31 30 694 41 44
Fax: +31 30 696 02 64
Dr. J.H.E. Arts – Dept. Target Organ Toxicology – TNO Voeding
Dr. Nanne Bloksma – Utrecht Institute for Pharmaceutical Sciences, Utrecht University
This project aimed to improve hazard identification of respiratory chemical allergens, as is presently being done by measuring proliferation and cytokine production in local lymph nodes and IgE in serum upon dermal application of the chemical in question. To this end respiratory allergy endpoints, induced by the respiratory allergen trimellitic anhydride (TMA), were characterised by whole genome analysis of lung tissue and blood proteomics. The endpoints were compared to those induced by the contact allergen dinitrochlorobenzene (DNCB). TMA induced up-regulation of genes for allergy-associated chemokines and inflammatory-associated genes including those associated with lung-remodelling. In addition, genes involved in down-sizing inflammation were activated. Bloodproteomics reflected activation of inflammation-down-sizing mechanisms. DNCB also up-regulated genes for allergy-associated chemokines, but not for lung remodelling and inflammation-down-sizing mechanisms.
It is concluded that parameters for lung remodelling are a promising tool in hazard identification of by low molecular weight (LMW) respiratory allergens. The results suggest also that, as long as inflammation-down-sizing mechanisms are present, chronic asthma may not occur.
CF Kuper, RH Stierum, A Boorsma, MA Schijf, M Prinsen, JP Bruijntjes, N Bloksma, JHE Arts, The contact allergen dinitrochlorobenzene (DNCB) and respiratory allergy in the Th2-prone Brown Norway rat, Toxicology 2008, 246, 213-221.
CF Kuper, WHM Heijne, M Dansen, KCM Verhoeckx, A Boorsma, M Radonjic, J Bruijntjes, R Stierum, H Muijser, JHE Arts, Molecular characterization of trimellitic anhydride-induced respiratory allergy in Brown Norway rats, Toxicologic Pathology 2008, 36: 985-998.
CF Kuper, M Radonjic, J van Triel, R Stierum, RJ de Groot, JHE Arts, Oxazolone (OXA) is a respiratory allergen in Brown Norway rats, Toxicology 2011, 290: 59-68.