TY - JOUR
T1 - Expression of interleukin-16 by human epithelial cells inhibition by dexamethasone
AU - Arima, Masafumi
AU - Plitt, Jim
AU - Stellato, Cristiana
AU - Bickel, Carol
AU - Motojima, Shinji
AU - Makino, Sohei
AU - Fukuda, Takeshi
AU - Schleimer, Robert P.
PY - 1999
Y1 - 1999
N2 - 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-1β, or tumor necrosis factor (TNF)-α whereas interferon-γ 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 TL-1β and TNF-α 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-1β, and TNF-α, 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.
AB - 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-1β, or tumor necrosis factor (TNF)-α whereas interferon-γ 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 TL-1β and TNF-α 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-1β, and TNF-α, 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.
UR - http://www.scopus.com/inward/record.url?scp=0033257937&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033257937&partnerID=8YFLogxK
U2 - 10.1165/ajrcmb.21.6.3671
DO - 10.1165/ajrcmb.21.6.3671
M3 - Article
C2 - 10572065
AN - SCOPUS:0033257937
SN - 1044-1549
VL - 21
SP - 684
EP - 692
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
IS - 6
ER -