Inhibition of Nitric Oxide and Tumor Necrosis Factor-α (TNF-α) Production by Propenone Compound through Blockade of Nuclear Factor (NF)-κB Activation in Cultured Murine Macrophages

2004 ◽  
Vol 27 (5) ◽  
pp. 617-620 ◽  
Author(s):  
Eung-Seok Lee ◽  
Hye Kyung Ju ◽  
Tae Churl Moon ◽  
Eunkyung Lee ◽  
Yurngdong Jahng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Nuclear Factor ◽  
Murine Macrophages ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Characterization of rabbit SP-B promoter region responsive to downregulation by tumor necrosis factor-α

2000 ◽  
Vol 279 (5) ◽  
pp. L806-L814 ◽  
Author(s):  
Kiflu Berhane ◽  
Ramgopal K. Margana ◽  
Vijayakumar Boggaram
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Promoter Activity ◽  
Tumor Necrosis Factor Α ◽  
Surfactant Protein ◽  
Nuclear Factor ◽  
Tnf Α ◽  
Nuclear Levels ◽  
Factor Α ◽  
Necrosis Factor

Surfactant protein B (SP-B) is essential for the maintenance of biophysical properties and physiological function of pulmonary surfactant. Tumor necrosis factor-α (TNF-α), an important mediator of lung inflammation, inhibits surfactant phospholipid and surfactant protein synthesis in the lung. In the present study, we investigated the TNF-α inhibition of rabbit SP-B promoter activity in a human lung adenocarcinoma cell line (NCI-H441). Deletion experiments indicated that the TNF-α response elements are located within −236 bp of SP-B 5′-flanking DNA. The TNF-α response region contained binding sites for nuclear factor-κB (NF-κB), Sp1/Sp3, thyroid transcription factor (TTF)-1, and hepatocyte nuclear factor (HNF)-3 transcription factors. Inhibitors of NF-κB activation such as dexamethasone and N-tosyl-l-phenylalanine chloromethyl ketone and mutation of the NF-κB element did not reverse TNF-α inhibition of SP-B promoter, indicating that TNF-α inhibition of SP-B promoter activity occurs independently of NF-κB activation. TNF-α treatment decreased the binding activities of TTF-1 and HNF-3 elements without altering the nuclear levels of TTF-1 and HNF-3α proteins. Pretreatment of cells with okadaic acid reversed TNF-α inhibition of SP-B promoter activity. Taken together these data indicated that in NCI-H441 cells 1) TNF-α 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-3α are not due to decreased nuclear levels of the proteins, and 3) okadaic acid-sensitive phosphatases may be involved in mediating TNF-α inhibition of SP-B promoter activity.

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