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Tumor Necrosis Factor Alpha Stimulation of Human Clara Cell Secretory Protein Production by Human Airway Epithelial Cells
Author(s) -
COWAN M. J.,
HUANG X.,
YAO X. L.,
SHELHAMER J. H.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb05530.x
Subject(s) - uteroglobin , tumor necrosis factor alpha , proinflammatory cytokine , respiratory epithelium , cell culture , cytokine , secretion , epithelium , biology , microbiology and biotechnology , messenger rna , chemokine , immunology , endocrinology , inflammation , gene , biochemistry , genetics
A bstract : 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‐α) 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‐α (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‐α 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‐α stimulation. A CCSP mRNA half‐life assay indicated that TNF‐α induced increases in CCSP mRNA at least in part at a posttranscriptional level. Therefore, TNF‐α induces airway epithelial cell expression of human CCSP and may modulate airway inflammatory responses in this manner.