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1 Department of Pulmonology, Leiden University Medical Center, 2300 RC Leiden; and 2 Department of Dermatology, University Hospital Nijmegen, 6500 HB Nijmegen, The Netherlands
Secretory leukocyte
proteinase inhibitor (SLPI) is a serine proteinase inhibitor that is
produced locally in the lung by cells of the submucosal bronchial
glands and by nonciliated epithelial cells. Its main function appears
to be the inhibition of neutrophil elastase (NE). Recently, NE was
found to enhance SLPI mRNA levels while decreasing SLPI protein release
in airway epithelial cells. Furthermore, glucocorticoids were shown to
increase both constitutive and NE-induced SLPI mRNA levels. In addition
to NE, stimulated neutrophils also release
-defensins. Defensins are
small, antimicrobial polypeptides that are found in high concentrations
in purulent secretions of patients with chronic airway inflammation.
Like NE, defensins induce interleukin-8 production in airway epithelial cells. This induction is sensitive to inhibition by the glucocorticoid dexamethasone and is prevented in the presence of
1-proteinase inhibitor. The aim of the present study was
to investigate the effect of defensins on the production of SLPI and
the related NE inhibitor elafin/SKALP in primary bronchial epithelial
cells (PBECs). Defensins significantly increase SLPI protein release by
PBECs in a time- and dose-dependent fashion without affecting SLPI mRNA
synthesis. In the presence of
1-proteinase inhibitor, the defensin-induced SLPI protein release is further enhanced, but no
effect was observed on SLPI mRNA levels. Dexamethasone did not affect
SLPI protein release from control or defensin-treated PBECs. In
addition, we observed a constitutive release of elafin/SKALP by PBECs,
but this was not affected by defensins. The present results suggest a
role for defensins in the dynamic regulation of the antiproteinase
screen in the lung at sites of inflammation.
secretory leukocyte proteinase inhibitor; inflammation; proteinase inhibitors
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