title: Allergen induced TFF2 is expressed by mucus-producing airway epithelial cells but is not a major regulator of inflammatory responses in the murine lung.
abstract: Asthma is a complex pulmonary disorder characterized by reversible airflow obstruction, airway hyperresponsiveness, mucus cell metaplasia, and inflammation. Employing animal models of pulmonary inflammation induced by different allergens and Th2 cytokines, the authors have previously described the up-regulation of trefoil factor 2 (TFF2) in the lung. Given the known biological role of trefoil factors in epithelial restitution, it has been postulated that allergen-induced TFF2 might have an important role in asthmatic responses. Here the authors show that TFF2 is induced early and maintained for 2 weeks following allergen challenge in the mouse lung. In situ mRNA hybridization demonstrated expression of TFF2 primarily in a subset of bronchial epithelial cells and TFF2 immunohistochemistry identified expression in alcian blue-positive bronchial epithelial cells. TFF2 gene-deleted mice inoculated with allergen displayed a 10-fold increase in total cellularity compared with saline controls. Although this response was modestly attenuated compared to wild type controls, the loss of TFF2 did not affect gross levels of tissue inflammation. Furthermore, the loss of TFF2 did not affect induction or resolution of mucus cell metaplasia as measured by periodic acid-Schiff (PAS) or alcian blue staining. Thus, TFF2 is an allergen-induced gene, which is expressed in mucus-positive airways, but is not a major contributor to allergen-induced goblet cell metaplasia, mucus production, or inflammatory responses in the lung.
authors.affiliation: Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Nikolaidis
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hogan
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics; D009093:Mucus / Q000276:immunology / Q000378:metabolism*; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D010455:Peptides / Q000235:genetics; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000071164:Trefoil Factor-2
chemical_list: D000485:Allergens; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D012333:RNA, Messenger; C481546:TFF2 protein, mouse; D000071164:Trefoil Factor-2