title: Interleukin-18 expression by alveolar epithelial cells type II in tuberculosis and sarcoidosis.
abstract: The aims of the present study were to characterize the localization of interleukin-18 (IL-18) expression in lung tissue specimens from patients with pulmonary tuberculosis, sarcoidosis and controls, and to determine whether human alveolar epithelial cells type II (AEC-II) are able to generate IL-18 in primary culture. IL-18 was determined using semiquantitative reverse-transcription-PCR and localized in lungs using in situ hybridization. IL-18 protein levels were determined using the enzyme-linked immunosorbent assay and western blot analysis. Alveolar epithelial cells type II (AEC-II) were stimulated in vitro by proinflammatory cytokines, lipopolysaccharides, and whole cell lysate from Mycobacterium tuberculosis. IL-18 mRNA expression was significantly increased in the lungs affected by tuberculosis and sarcoidosis. In situ hybridization revealed different sites of expression in tuberculosis and sarcoidosis lungs, with AEC-II as one major source of IL-18 in the alveolar compartment. Basal IL-18 expression could be detected in normal AEC-II. Whole cell lysate from M. tuberculosis, but not lipopolysaccharide, led to a strong increase of IL-18 mRNA accumulation in AEC-II. Resting AEC-II secreted only small amounts of IL-18, but intracellular IL-18 protein levels increased in a time-dependent manner during culture. Proinflammatory cytokines tumour necrosis factor-alpha, IL-1beta, and interferon-gamma altered IL-18 mRNA expression and mature protein secretion of human AEC-II. These findings indicate a possible role for AEC-II and AEC-II-derived IL-18 in pathomechanisms of granulomatous lung diseases.
authors.affiliation: Department of Pneumology, Medical Center, Albert-Ludwigs University, Freiburg, Germany. petchkov@interchange.ubc.ca
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Pechkovsky
authors.forename: Torsten
authors.initials: T
authors.lastname: Goldmann
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Vollmer
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller-Quernheim
authors.forename: Gernot
authors.initials: G
authors.lastname: Zissel
mesh_terms: D016207:Cytokines / Q000494:pharmacology; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D006801:Humans; D020382:Interleukin-18 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D021381:Protein Transport; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017565:Sarcoidosis, Pulmonary / Q000235:genetics / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D020382:Interleukin-18; D008070:Lipopolysaccharides; D012333:RNA, Messenger