Expression of interleukin-16 by human epithelial cells - Inhibition by dexamethasone

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 (lympho cyte chemoattractant factor) was reported to be a potent chemotactic stimul us for CD4(+) T lymphocytes and eosinophils, the types of leukocyte found i n the proximity of bronchial epithelium in asthmatic individuals. To test t he possibility that bronchial epithelial cells produce IL-16, we analyzed R NA and culture supernatants fi om the human bronchial epithelial cell line BEAS-2B, using reverse transcription-polymerase chain reaction and enzyme-l inked immunosorbent assay, respectively. BEAS-2B constitutively expressed I L-16 messenger RNA (mRNA) and protein; IL-16 expression was significantly u pregulated in a concentration-dependent manner within 24 h by stimulation w ith histamine, IL-16, or tumor necrosis factor (TNF)-alpha whereas interfer on-gamma did not significantly increase IL-16. Findings in BEAS-2B cells we re confirmed in primary bronchial epithelial cells. Using TA cloning, IL-16 was cloned from BEAS-2B airway epithelial cells. Sequence analysis confine d its near identity with lymphocyte-derived IL-16. The combination of IL-1 beta and TNF-alpha had an additive effect on IL-16 expression. This combina tion 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 comb ined cytokines was significantly inhibited by pretreatment with the protein synthesis inhibitor cycloheximide (10 mu g/ml). Pretreatment with dexameth asone also significantly suppressed the expression of IL-16, in a concentra tion-dependent manner. Sputum samples from asthmatic subjects were found to have higher levels of IL-16 than were samples from subjects with other pul monary inflammatory diseases. These findings suggest that bronchial epithel ial cells have the capacity to produce IL-16 after stimulation with histami ne, IL-1 beta, and TNF-alpha, and raise the possibility that epithelium-der ived IL-16 may play a role in recruitment of eosinophils and CD4(+) T lymph ocytes in the airways. Downregulution of IL-16 expression by dexamethasone suggests that glucocorticoids may inhibit airway inflammation partly by sup pressing the synthesis of inflammatory cytokines including IL-16. Arima, M. , J, Plitt, C. Stellato, C. Bickel, S. Motojima, S. Makino, T. Fukuda, and R. P. Schleimer. 1999. Expression of interleukin-16 by human epithelial cel ls: inhibition by dexamethasone.