PMID- 9761760
OWN - NLM
STAT- MEDLINE
DCOM- 19981105
LR  - 20111117
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 19
IP  - 4
DP  - 1998 Oct
TI  - Tumor necrosis factor-alpha stimulates human Clara cell secretory protein 
      production by human airway epithelial cells.
PG  - 629-35
AB  - Clara cell secretory protein (CCSP), or CC10, is an inhibitor of secretory 
      phospholipase A2 which may be produced by phagocytic cells and by a variety of 
      other cells in the airway. Tumor necrosis factor-alpha (TNF-alpha) 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 TNF-alpha (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 TNF-alpha 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 TNF-alpha-induced increases in CCSP gene expression are 
      regulated at the post-transcriptional level. We conclude that TNF-alpha induces 
      airway epithelial cell expression of human CCSP protein and may modulate airway 
      inflammatory responses in this manner.
FAU - Yao, X L
AU  - Yao XL
AD  - Critical Care Medicine Department, Clinical Center, National Institutes of 
      Health, Bethesda, Maryland, USA.
FAU - Levine, S J
AU  - Levine SJ
FAU - Cowan, M J
AU  - Cowan MJ
FAU - Logun, C
AU  - Logun C
FAU - Shelhamer, J H
AU  - Shelhamer JH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Carcinogens)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (SCGB1A1 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9060-09-7 (Uteroglobin)
SB  - IM
MH  - Bronchi/*cytology
MH  - Carcinogens/metabolism
MH  - Cell Line, Transformed/metabolism
MH  - Epithelial Cells/cytology/*metabolism
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Proteins/*genetics
MH  - RNA, Messenger/metabolism
MH  - Transcription, Genetic
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - *Uteroglobin
EDAT- 1998/10/08 00:00
MHDA- 1998/10/08 00:01
CRDT- 1998/10/08 00:00
PHST- 1998/10/08 00:00 [pubmed]
PHST- 1998/10/08 00:01 [medline]
PHST- 1998/10/08 00:00 [entrez]
AID - 10.1165/ajrcmb.19.4.3129 [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 1998 Oct;19(4):629-35. doi: 10.1165/ajrcmb.19.4.3129.