%0 Journal Article
%T Differential Cell Sensitivity between OTA and LPS upon Releasing TNF-汐
%A Lauy Al-Anati
%A Ebtisam Essid
%A Ulla Stenius
%A Knut Beuerlein
%A Klaus Schuh
%A Ernst Petzinger
%J Toxins
%D 2010
%I MDPI AG
%R 10.3390/toxins2061279
%X The release of tumor necrosis factor 汐 (TNF-汐) by ochratoxin A (OTA) was studied in various macrophage and non-macrophage cell lines and compared with E. coli lipopolysaccharide (LPS) as a standard TNF-汐 release agent. Cells were exposed either to 0, 2.5 or 12.5 米mol/L OTA, or to 0.1 米g/mL LPS, for up to 24 h. OTA at 2.5 米mol/L and LPS at 0.1 米g/mL were not toxic to the tested cells as indicated by viability markers. TNF-a was detected in the incubated cell medium of rat Kupffer cells, peritoneal rat macrophages, and the mouse monocyte macrophage cell line J774A.1: TNF-a concentrations were 1,000 pg/mL, 1,560 pg/mL, and 650 pg/mL, respectively, for 2.5 米mol/L OTA exposure and 3,000 pg/mL, 2,600 pg/mL, and 2,115 pg/mL, respectively, for LPS exposure. Rat liver sinusoidal endothelial cells, rat hepatocytes, human HepG2 cells, and mouse L929 cells lacked any cytokine response to OTA, but showed a significant release of TNF-a after LPS exposure, with the exception of HepG2 cells. In non-responsive cell lines, OTA lacked both any activation of NF-百B or the translocation of activated NF-百B to the cell nucleus, i.e., in mouse L929 cells. In J774A.1 cells, OTA mediated TNF-a release via the pRaf/MEK 1/2每NF-百B and p38-NF-百B pathways, whereas LPS used pRaf/MEK 1/2-NF-百B, but not p38-NF-百B pathways. In contrast, in L929 cells, LPS used other pathways to activate NF-百B. Our data indicate that only macrophages and macrophage derived cells respond to OTA and are considered as sources for TNF-a release upon OTA exposure.
%K ochratoxin A
%K lipopolysaccharide
%K tumor necrosis factor 汐
%K Kupffer cells
%K macrophages
%K rat liver sinusoidal endothelial cells
%K HepG2 cells
%K rat hepatocytes
%U http://www.mdpi.com/2072-6651/2/6/1279