Abstract
Asthma is a heterogeneous lung disorder characterized by airway obstruction, inflammation and eosinophil infiltration into the lung. Both genetics and environmental factors influence the expression of asthma, and not all asthma is the result of a specific immune response to allergen. Numerous asthma phenotypes have been described, including occupational asthma, and therapeutic strategies for asthma control are similar regardless of phenotype. We hypothesized that mechanistic pathways leading to asthma symptoms in the effector phase of the disorder differ with the inciting allergen. Since route of allergen exposure can influence mechanistic pathways, mice were sensitized by identical routes with a high molecular weight occupational allergen ovalbumin and a low molecular weight occupational allergen trimellitic anhydride (TMA). Different statistical methods with varying selection criteria resulted in identification of similar candidate genes. Array data are intended to provide candidate genes for hypothesis generation and further experimentation. Continued studies focused on genes showing minimal changes in the TMA-induced model but with clear up-regulation in the ovalbumin model. Two of these genes, arginase 1 and eotaxin 1 are the focus of continuing investigations in mouse models of asthma regarding differences in mechanistic pathways depending on the allergen. Microarray data from the ovalbumin and TMA model of asthma were also compared to previous data usingAspergillus as allergen to identify putative asthma ‘signature genes’, i.e. genes up-regulated with all 3 allergens. Array studies provide candidate genes to identify common mechanistic pathways in the effector phase, as well as mechanistic pathways unique to individual allergens.
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References
Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention (GINA). Bethesda: National Institutes of Health, National Heart Lung and Blood Institute: 2002. Report No 02-3659.
Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet. 2006;368:804–813.
Lancet editorial. A plea to abandon asthma as a disease concept. Lancet. 2006;368:705.
Morley J. Inflammation and asthma therapy: a false dawn. Pulm Pharmacol Ther. 2006;19:200–204.
Jenkins HA, Cherniack R, Szefler SJ, Covr R, Gelfand EW, Spahn JD. A comparison of the clinical characteristics of children and adults with severe asthma. Chest. 2003;124:1318–1324.
Bernstein IL, Bernstein DI, Chan-Yeung M, Malo JL. Definition and classification of asthma in the workplace. In: Bernstein IL, Chan-Yeung M, Malo JL, Bernstein DI editors. Asthma in the Workplace, 3rd ed. New York: Taylor & Francis; 2006. p. 1–8.
Smith AB, Bernstein DI, London MA, Gallagher J, Ornella GA, Gelletly SK, et al. Evaluation of occupational asthma from airborne egg protein exposure in multiple settings. Chest. 1990;98:398–404.
Boeniger MF, Lummus ZL, Biagini RE, Bernstein DI, Swanson MC, Reed C, et al. Exposure to protein aeroallergens in egg processing facilities. Appl Occup Environ Hyg. 2001;16:660–670.
Escudero C, Quirce S, Fernandez-Nieto M, de Miguel J, Cuesta J, Sastre J. Egg white proteins as inhalant allergens associated with baker’s asthma. Allergy. 2003;58:616–620.
Wisnewski AV, Redlich CA, Mapp CE, Bernstein DI. Polyisocyanates and their prepolymers. In: Bernstein IL, Chan-Yeung M, Malo JL, Bernstein DI editors. Asthma in the Workplace, 3rd ed. New York: Taylor & Francis: 2006. p. 481–504.
Zeiss CR, Patterson R, Pruzansky JJ, Miller MM, Rosenberg M, Levitz D. Trimellitic anhydride-induced airway syndromes: Clinical and immunologic studies. J Allergy Clin Immunol. 1977;60:96–103.
Karp CL, Grupe A, Schadt E, Ewart SL, Keane-Moore M, Cuomo PJ, et al. Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma. Nature Immunol. 2000;1:221–226.
Zimmermann N, King NE, Laporte J, Yang M, Mishra A, Pope SM, et al. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Investigation. 2003;111:1863–1874.
Yang M, Rangasamy D, Matthaei KI, Frew AJ, Zimmermann N, Mahalingam S, et al. Inhibition of arginase I activity by RNA interference attenuates IL-13-induced airways hyper-responsiveness. J Immunol. 2006;177:5595–5603.
King NE, Zimmermann N, Pope SM, Fulkerson PC, Nikolaidis NM, Mishra A, et al. Expression and regulation of a disintegrin and metalloproteinase (ADAM) 8 in experimental asthma. Am J Respir Cell Mol Biol. 2004;31:257–265.
Nikolaidis NM, Zimmermann N, King NE, Mishra A, Pope SM, Finkelman FD, et al. Trefoil factor-2 is an allergen induced gene regulated by Th2 cytokines and STAT6 in the lung. Am J Respir Cell Mol Biol. 2003;29:458–464.
Zimmermann N, Doepker MP, Witte DP, Stringer KF, Fulkerson PC, Pope SM, et al. Expression and regulation of small proline-rich protein 2 in allergic inflammation. Am J Respir Cell Mol Biol. 2005;32:428–435.
Zimmermann N, Mishra A, King NE, Fulerson PC, Doepker MP, Nikolaidis NM, et al. Transcript signatures in experimental asthma: Identification of STAT6-dependent and-independent pathways. J Immunol. 2004;172:1815–1824.
Regal JF. Immunologic effector mechanisms in animal models of occupational asthma. J Immunotoxicology. 2004;1:25–38.
Brewer JP, Kisselgof AB, Martin TR. Genetic variability in pulmonary physiological, cellular, and antibody responses to antigen in mice. Am J Respir Crit Care Med. 1999;160:1150–1156.
Saito H, Abe J, Matsumoto K. Allergy-related genes in microarray: An update review. J Allergy Clin Immunol. 2005;116:56–59.
Greene AL, Rutherford MS, Regal RR, Flickinger GH, Hendrickson JA, Giulivi C, et al. Arginase activity differs with allergen in the effector phase of ovalbumin-versus trimellitic anhydride-induced asthma. Toxicol Sci. 2005;88: 420–433.
Cui X, Churchill G. A. How many mice and how many arrays? Replication in mouse cDNA microarray experiments. In: Johnson KF, Lin SM editors. Methods of Microarray Data Analysis III. Norwell, MA: Kluwer Academic Publishers; 2003. p. 139–154.
Storey JD, Tibshirani R. Statistical significance for genome-wide studies. Proc Natl Acad Sci USA. 2003;100:9440–9445.
Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP. Summaries of Affymetrix genechip probe level data. Nucleic Acids Res. 2003;31:e15.
Smyth GK. Linear Models and Empirical Bayes Methods for assessing differential expression in microarray experiments. Statistical Applications in Genetics and Molecular Biology. 2004;3:Issue 1, article 3. Available at:http://www.bepress.com/sagmb/vol3/iss1/art3.
Malerba G, Pignatti PF. A review of asthma genetics: gene expression studies and recent candidates. J Appl Genet. 2005; 46:93–104.
Rolph MS, Sisavanh M, Liu SM, Mackay CR. Clues to asthma pathogenesis from microarray expression studies. Pharmacol & Therapeutics. 2006;109:284–294.
Hansel NN, Diette GB. Gene expression profiling in human asthma. Proc Am Thorac Soc. 2007;4:32–36.
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Regal, J.F., Greene, A.L. & Regal, R.R. Mechanisms of occupational asthma: Not all allergens are equal. Environ Health Prev Med 12, 165–171 (2007). https://doi.org/10.1007/BF02897986
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DOI: https://doi.org/10.1007/BF02897986