Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
"To test the hypothesis that fluid flow alters NF-kappaB activation and expression of cell adhesion molecules in osteoblastic cells, we examined the effect of
oscillating fluid flow (OFF)
on tumor necrosis factor (TNF)-alpha-induced NF-kappaB activation in rat osteoblast-like UMR106 cells.
We found that OFF inhibits NF-kappaB-DNA binding activities, especially TNF-alpha -induced p50-p65 heterodimer NF-kappaB activation and TNF-alpha -induced intercellular adhesion molecule-1 mRNA expression.
The inhibitory effects of OFF on both TNF-alpha -induced NF-kappaB activation and intercellular adhesion molecule-1 mRNA expression were shear stress-dependent and also increased with OFF exposure duration, indicating that OFF has potent effects on mechanotransduction pathways.
OFF also inhibited TNF-alpha -induced IkappaBalpha degradation and TNF-alpha -induced IkappaB kinase (IKK) activity in a shear stress-dependent manner.
These results demonstrate that IKK is an initial target molecule for OFF effects on osteoblastic cells.
Thus, OFF inhibits TNF-alpha -induced IKK activation, leading to a decrease in phosphorylation and degradation of inhibitory IkappaBalpha , which in turn results in the decrease of TNF-alpha -induced NF-kappaB activation and potentially the transcription of target genes. J. Biol. Chem. (2001)
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