Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Clara cell secretory protein (CCSP) or uteroglobin/CC10 is a
product of epithelial cells in a variety of organs including
the lung. CCSP has anti-inflammatory properties and may act
as an inhibitor of secretory phospholipase A
2's. Tumor necrosis
factor alpha (TNF-
) is capable of inducing the expression of
gene products including a variety of cytokines and chemokines
in the airway epithelium that may upregulate the airway inflammatory
response. Therefore, it was of interest to determine whether
this proinflammatory cytokine might also induce the production
of a counterregulatory protein such as CCSP, which might modulate
the inflammatory response in the airway. Normal human tracheobronchial
epithelial cells in primary culture and a human bronchial epithelial
cell line (BEAS-2B) were studied. CCSP mRNA levels in BEAS-2B
cells were detected by ribonuclease protection assay. CCSP mRNA
levels increased in response to TNF-
(20 ng/mL) stimulation
after 8-36 h, with the peak increase at 18 h. Immunoblotting
of CCSP released from BEAS-2B cells into the culture media demonstrated
that TNF-
induced the synthesis and secretion of CCSP over 8
to 18 h. Similarly, TNF stimulated the release of CCSP from
human tracheobronchial epithelial cells in primary culture at
8 and 18 h. The CCSP reporter gene including 801 bases 5' of
the transcription start site did not increase transcriptional
activity in response to TNF-
stimulation. A CCSP mRNA half-life
assay indicated that TNF-
induced increases in CCSP mRNA at
least in part at a posttranscriptional level. Therefore, TNF-
induces airway epithelial cell expression of human CCSP and
may modulate airway inflammatory responses in this manner.
