Asthma and the CCAAT-enhancer binding proteins: a holistic view on airway inflammation and remodeling.
Asthma is an airway disease with increasing prevalence characterized by intermittent reversible airway obstruction, airway inflammation, and airway wall remodeling. The disease is generally triggered by inhalation of allergens, but nonallergic asthma triggers are quite common. The pathogenesis of asthma is well documented, and a great deal of research has been carried out to elucidate the underlying mechanisms. A multitude of articles have focused on cells alleged to be involved in the pathogenesis, including circulating cells from the immunologic compartment (ie, eosinophils and T lymphocytes) and resident cells, such as fibroblasts, airway smooth muscle cells, and, more recently, the airway epithelium. Despite the enormous amount of research, it is still unclear what exactly causes asthma. A general feature of most studies is an enhanced activation status of asthmatic cells, suggesting a general defect with respect to regulation of cellular responses. Here we discuss the ubiquitous transcription factor family of CCAAT-enhancer binding proteins (C/EBPs) and its involvement in inflammation and proliferation. We propose that an imbalance of C/EBP isoform expression might lead to an enhanced activity of asthmatic cells and provide an overall hypothesis that both airway inflammation and remodeling can be conceived as the result of an imbalance of C/EBP isoform expression.
Borger
Peter
P
Department of Pharmacology and the Woolcock Institute of Medical Research, Royal Prince Alfred Hospital, University of Sydney, Australia.
Black
Judith L
JL
Roth
Michael
M
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D001249:Asthma / Q000209:etiology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D002453:Cell Cycle; D006801:Humans; D020033:Protein Isoforms; D018418:Th2 Cells / Q000276:immunology; D014157:Transcription Factors / Q000502:physiology
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D022762:CCAAT-Enhancer-Binding Proteins; D020033:Protein Isoforms; D014157:Transcription Factors