title: Increased production and immunohistochemical localization of transforming growth factor-beta in idiopathic pulmonary fibrosis.
abstract: Transforming growth factor-beta (TGF-beta) can regulate cell growth and differentiation as well as production of extracellular matrix proteins. Elevated production of TGF-beta has been associated with human and rodent chronic inflammatory and fibrotic diseases. Using immunohistochemical staining, we have examined lung sections of patients with advanced idiopathic pulmonary fibrosis (IPF), a disease characterized by chronic inflammation and fibrosis and demonstrated a marked and consistent increase in TGF-beta production in epithelial cells and macrophages when compared to patients with nonspecific inflammation and those with no inflammation or fibrosis. In patients with advanced IPF, intracellular staining with anti-LC (1-30) TGF-beta antibody was seen prominently in bronchiolar epithelial cells. In addition, epithelial cells of honeycomb cysts and hyperplastic type II pneumocytes stained intensely. Anti-CC (1-30) TGF-beta antibody, which reacts with extracellular TGF-beta, was localized in the lamina propria of bronchioles and in subepithelial regions of honeycomb cysts in areas of dense fibroconnective tissue deposition. The close association of subepithelial TGF-beta to the intracellular form in advanced IPF suggests that TGF-beta was produced and secreted primarily by epithelial cells. Because of the well-known effects of TGF-beta on extracellular matrix formation and on epithelial cell differentiation, the increased production of TGF-beta in advanced IPF may be pathogenic to the pulmonary fibrotic and regenerative responses seen in this disease.
authors.affiliation: Manitoba Institute of Cell Biology, Department of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Khalil
authors.forename: R N
authors.initials: RN
authors.lastname: O'Connor
authors.forename: H W
authors.initials: HW
authors.lastname: Unruh
authors.forename: P W
authors.initials: PW
authors.lastname: Warren
authors.forename: K C
authors.initials: KC
authors.lastname: Flanders
authors.forename: A
authors.initials: A
authors.lastname: Kemp
authors.forename: O H
authors.initials: OH
authors.lastname: Bereznay
authors.forename: A H
authors.initials: AH
authors.lastname: Greenberg
mesh_terms: D001706:Biopsy; D006801:Humans; D007150:Immunohistochemistry; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta