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In vitro allergen challenge of peripheral blood induces differential gene expression in mononuclear cells of asthmatic patients: inhibition of cytosolic phospholipase A 2α overcomes the asthma‐associated response
Author(s) -
Whalen K. A.,
Legault H.,
Hang C.,
Hill A.,
Kasaian M.,
Donaldson D.,
Bensch G. W.,
Bensch G.,
Baker J.,
Reddy P. S.,
Wood N.,
Ramarao M. K.,
Ellis D. K.,
Csimma C.,
McKee C.,
Clark J. D.,
Ryan J.,
Dorner A. J.,
O'Toole M.
Publication year - 2008
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2008.03059.x
Subject(s) - peripheral blood mononuclear cell , immunology , asthma , leukotriene , allergen , gene expression , medicine , allergy , arachidonate 5 lipoxygenase , phospholipase a2 , arachidonic acid , biology , in vitro , gene , enzyme , biochemistry
Summary Background Existing treatments for asthma are not effective in all patients and disease exacerbations are common, highlighting the need for increased understanding of disease mechanisms and novel treatment strategies. The leukotriene pathway including the enzyme responsible for arachidonic acid release from cellular phospholipids, cPLA 2 α, is a major contributor to asthmatic responses and an attractive target in asthma therapies. Objective The study reported here investigates (a) the differential effects of in vitro exposure of peripheral blood mononuclear cells (PBMCs) to allergen between asthma and healthy subjects, and (b) the contribution of cPLA 2 α to these differences in gene expression. Methods In vitro responses of asthma ( N =26) and healthy ( N =11) subject PBMC samples to allergen stimulation in the presence and absence of cPLA 2 α inhibition or 5‐lipoxygenase inhibition were compared at the gene expression level using oligonucleotide arrays and at the protein level using ELISA. Results Subject samples within both asthma and healthy groups showed allergen‐dependent cytokine production and allergen‐dependent gene expression changes, although transcriptional profiling identified 153 genes that were modulated significantly differently by allergen between asthma and healthy subjects. Among these were genes previously associated with asthma, but the majority (about 80%) have not previously been associated with asthma. Conclusions Transcriptional profiling elucidated novel gene expression differences between the asthmatic and healthy subject samples. Although 5‐lipoxygenase inhibition did not significantly affect allergen‐modulated gene expression, the inhibition of cPLA 2 α activity affected many of the allergen‐dependent, asthma‐associated gene expression changes.