Am. J. Respir. Cell Mol. Biol.,
Volume 21, Number 6, December, 1999 684-692
Expression of Interleukin-16 by Human Epithelial Cells
Inhibition by Dexamethasone
Masafumi
Arima,
Jim
Plitt,
Cristiana
Stellato,
Carol
Bickel,
Shinji
Motojima,
Sohei
Makino,
Takeshi
Fukuda,
and
Robert P.
Schleimer
Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and
Dokkyo University School of Medicine, Mibu, Tochigi, Japan
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-1 , or tumor necrosis factor (TNF)- whereas interferon- 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-1 and TNF- 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 µg/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-1 , and TNF- , 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.
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Copyright © 1999 American Thoracic Society.
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