title: Expression of interleukin-16 by human epithelial cells. Inhibition by dexamethasone.
abstract: Production of chemoattractants by bronchial epithelial cells may contribute to the local accumulation of inflammatory cells in patients with bronchial asthma and other pulmonary diseases. Recently, interleukin (IL)-16 (lymphocyte chemoattractant factor) was reported to be a potent chemotactic stimulus for CD4(+) T lymphocytes and eosinophils, the types of leukocyte found in the proximity of bronchial epithelium in asthmatic individuals. To test the possibility that bronchial epithelial cells produce IL-16, we analyzed RNA and culture supernatants from the human bronchial epithelial cell line BEAS-2B, using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. BEAS-2B constitutively expressed IL-16 messenger RNA (mRNA) and protein; IL-16 expression was significantly upregulated in a concentration-dependent manner within 24 h by stimulation with histamine, IL-1beta, or tumor necrosis factor (TNF)-alpha whereas interferon-gamma did not significantly increase IL-16. Findings in BEAS-2B cells were confirmed in primary bronchial epithelial cells. Using TA cloning, IL-16 was cloned from BEAS-2B airway epithelial cells. Sequence analysis confirmed its near identity with lymphocyte-derived IL-16. The combination of IL-1beta and TNF-alpha had an additive effect on IL-16 expression. This combination of cytokines also had a priming effect on histamine-induced IL-16 mRNA expression, which was observed within 24 h and which increased to at least 48 h after stimulation. The IL-16 expression induced by histamine and combined cytokines was significantly inhibited by pretreatment with the protein synthesis inhibitor cycloheximide (10 microg/ml). Pretreatment with dexamethasone also significantly suppressed the expression of IL-16, in a concentration-dependent manner. Sputum samples from asthmatic subjects were found to have higher levels of IL-16 than were samples from subjects with other pulmonary inflammatory diseases. These findings suggest that bronchial epithelial cells have the capacity to produce IL-16 after stimulation with histamine, IL-1beta, and TNF-alpha, and raise the possibility that epithelium-derived IL-16 may play a role in recruitment of eosinophils and CD4(+) T lymphocytes in the airways. Downregulation of IL-16 expression by dexamethasone suggests that glucocorticoids may inhibit airway inflammation partly by suppressing the synthesis of inflammatory cytokines including IL-16.
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: M
authors.initials: M
authors.lastname: Arima
authors.forename: J
authors.initials: J
authors.lastname: Plitt
authors.forename: C
authors.initials: C
authors.lastname: Stellato
authors.forename: C
authors.initials: C
authors.lastname: Bickel
authors.forename: S
authors.initials: S
authors.lastname: Motojima
authors.forename: S
authors.initials: S
authors.lastname: Makino
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
authors.forename: R P
authors.initials: RP
authors.lastname: Schleimer
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000276:immunology; D001980:Bronchi; D001987:Bronchiectasis / Q000276:immunology; D001988:Bronchiolitis / Q000276:immunology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D019410:Interleukin-16 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013183:Sputum / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D019410:Interleukin-16; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003907:Dexamethasone; D006632:Histamine; D003513:Cycloheximide