Clara cell secretory protein (CCSP), or CC10, is an inhibitor of secretory phospholipase A 2 which may be produced by phagocytic cells and by a variety of other cells in the airway. Tumor necrosis factor a (TNFa) is capable of activating phospholipases and inducing the expression of a variety of genes in the airway epithelium
which may modulate the airway inflammatory response. Therefore, it was of interest to determine
whether this proinflammatory cytokine could induce the production of a counterregulatory protein such as
CCSP which might modulate the production of eicosanoid mediators in the airway. Using a human bronchial
epithelial cell line (BEAS-2B), CCSP messenger RNA (mRNA) levels were detected by ribonuclease
protection assay. TNF treatment of these cells increased CCSP mRNA levels in a time- and dose-dependent
manner. The CCSP mRNA level increased in response to TNFa
(20 ng/ml) stimulation after 8 to 36 h with
the peak increase at 18 h. Immunoblotting of CCSP protein released into the culture media demonstrated
that TNFa induced the synthesis and secretion of CCSP protein in a time-dependent manner over 8 to 18 h.
The results of a CCSP reporter gene activity assay, nuclear run-on assay, and CCSP mRNA half-life assay
indicated that the TNFa -induced increases in CCSP gene expression are regulated at the post-transcriptional level. We conclude that TNFa induces airway epithelial cell expression of human CCSP protein and may modulate airway inflammatory responses in this manner. Yao, X. L., S. J. Levine, M. J. Cowan, C.
Logun, and J. H. Shelhamer. 1998. Tumor necrosis factora stimulates human Clara cell secretory protein production by human airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 19:629–635.