Toxins 2010, 2(6), 1279-1299; doi:10.3390/toxins2061279
Article

Differential Cell Sensitivity between OTA and LPS upon Releasing TNF-α

1,2email, 1, 2, 3, 1 and 1,* email
Received: 6 May 2010; in revised form: 28 May 2010 / Accepted: 28 May 2010 / Published: 1 June 2010
(This article belongs to the Special Issue Ochratoxins)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: The release of tumor necrosis factor α (TNF-α) 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-α release agent. Cells were exposed either to 0, 2.5 or 12.5 µmol/L OTA, or to 0.1 µg/mL LPS, for up to 24 h. OTA at 2.5 µmol/L and LPS at 0.1 µg/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 µmol/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-κB or the translocation of activated NF-κB 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–NF-κB and p38-NF-κB pathways, whereas LPS used pRaf/MEK 1/2-NF-κB, but not p38-NF-κB pathways. In contrast, in L929 cells, LPS used other pathways to activate NF-κB. 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.
Keywords: ochratoxin A; lipopolysaccharide; tumor necrosis factor α; Kupffer cells; macrophages; rat liver sinusoidal endothelial cells; HepG2 cells; rat hepatocytes
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MDPI and ACS Style

Al-Anati, L.; Essid, E.; Stenius, U.; Beuerlein, K.; Schuh, K.; Petzinger, E. Differential Cell Sensitivity between OTA and LPS upon Releasing TNF-α. Toxins 2010, 2, 1279-1299.

AMA Style

Al-Anati L, Essid E, Stenius U, Beuerlein K, Schuh K, Petzinger E. Differential Cell Sensitivity between OTA and LPS upon Releasing TNF-α. Toxins. 2010; 2(6):1279-1299.

Chicago/Turabian Style

Al-Anati, Lauy; Essid, Ebtisam; Stenius, Ulla; Beuerlein, Knut; Schuh, Klaus; Petzinger, Ernst. 2010. "Differential Cell Sensitivity between OTA and LPS upon Releasing TNF-α." Toxins 2, no. 6: 1279-1299.

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