PMID- 11053014
OWN - NLM
STAT- MEDLINE
DCOM- 20001109
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 279
IP  - 5
DP  - 2000 Nov
TI  - Characterization of rabbit SP-B promoter region responsive to downregulation by 
      tumor necrosis factor-alpha.
PG  - L806-14
AB  - Surfactant protein B (SP-B) is essential for the maintenance of biophysical 
      properties and physiological function of pulmonary surfactant. Tumor necrosis 
      factor-alpha (TNF-alpha), an important mediator of lung inflammation, inhibits 
      surfactant phospholipid and surfactant protein synthesis in the lung. In the 
      present study, we investigated the TNF-alpha inhibition of rabbit SP-B promoter 
      activity in a human lung adenocarcinoma cell line (NCI-H441). Deletion 
      experiments indicated that the TNF-alpha response elements are located within 
      -236 bp of SP-B 5'-flanking DNA. The TNF-alpha response region contained binding 
      sites for nuclear factor-kappa B (NF-kappa B), Sp1/Sp3, thyroid transcription 
      factor (TTF)-1, and hepatocyte nuclear factor (HNF)-3 transcription factors. 
      Inhibitors of NF-kappa B activation such as dexamethasone and 
      N-tosyl-L-phenylalanine chloromethyl ketone and mutation of the NF-kappa B 
      element did not reverse TNF-alpha inhibition of SP-B promoter, indicating that 
      TNF-alpha inhibition of SP-B promoter activity occurs independently of NF-kappa B 
      activation. TNF-alpha treatment decreased the binding activities of TTF-1 and 
      HNF-3 elements without altering the nuclear levels of TTF-1 and HNF-3 alpha 
      proteins. Pretreatment of cells with okadaic acid reversed TNF-alpha inhibition 
      of SP-B promoter activity. Taken together these data indicated that in NCI-H441 
      cells 1) TNF-alpha inhibition of SP-B promoter activity may be caused by 
      decreased binding activities of TTF-1 and HNF-3 elements, 2) the decreased 
      binding activities of TTF-1 and HNF-3 alpha are not due to decreased nuclear 
      levels of the proteins, and 3) okadaic acid-sensitive phosphatases may be 
      involved in mediating TNF-alpha inhibition of SP-B promoter activity.
FAU - Berhane, K
AU  - Berhane K
AD  - Department of Molecular Biology, University of Texas Health Science Center at 
      Tyler, Tyler, Texas 75708-3154, USA.
FAU - Margana, R K
AU  - Margana RK
FAU - Boggaram, V
AU  - Boggaram V
LA  - eng
GR  - HL-48048/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (FOXA1 protein, human)
RN  - 0 (Hepatocyte Nuclear Factor 3-alpha)
RN  - 0 (NF-kappa B)
RN  - 0 (NKX2-1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteolipids)
RN  - 0 (Pulmonary Surfactants)
RN  - 0 (Thyroid Nuclear Factor 1)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 6QYI7Y8OBO (mitopodozide)
RN  - 9000-55-9 (Podophyllin)
RN  - L36H50F353 (Podophyllotoxin)
SB  - IM
MH  - Adenocarcinoma
MH  - Animals
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cytosol/metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Hepatocyte Nuclear Factor 3-alpha
MH  - Humans
MH  - Lung Neoplasms
MH  - Mutagenesis, Site-Directed
MH  - NF-kappa B/metabolism
MH  - Nuclear Proteins/metabolism
MH  - Podophyllin/*analogs & derivatives/metabolism
MH  - Podophyllotoxin/analogs & derivatives
MH  - *Promoter Regions, Genetic
MH  - Proteolipids/*genetics
MH  - Pulmonary Surfactants/*genetics
MH  - Rabbits
MH  - Thyroid Nuclear Factor 1
MH  - Transcription Factors/metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2000/10/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/29 11:00
PHST- 2000/10/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/29 11:00 [entrez]
AID - 10.1152/ajplung.2000.279.5.L806 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2000 Nov;279(5):L806-14. doi: 
      10.1152/ajplung.2000.279.5.L806.