Journal article

Publication year: 2015

Pages: 3840-3848

Journal: Journal of Dairy Science

Volume number: 98

Issue number: 6

ISSN: 0022-0302

Open access status: Bronze

DOI Link: https://doi.org/10.3168/jds.2014-9044

Publisher: Elsevier

Abstract: 
Carnitine uptake into tissues is mediated mainly by the novel organic cation transporter 2 (OCTN2), whose expression is upregulated in the liver of early-lactating dairy cows. It has been shown recently that pro-inflammatory cytokines, including tumor necrosis factor a (TNF alpha), stimulate OCTN2 expression and carnitine uptake in intestinal cells and inflamed intestinal mucosa. Given that many early-lactating dairy cows show typical signs of hepatic and systemic inflammation, such as elevated concentrations of circulating TNF alpha and activation of the key regulator of inflammation, nuclear factor-kappa B (NF-kappa B), in tissues, it is possible that upregulation of OCTN2 and increase of carnitine uptake by TNF alpha is mediated by NF-kappa B, a mechanism that might contribute to the upregulation of OCNT2 in the liver of early-lactating dairy cows. Thus, in the present study, we tested the hypothesis that TNF alpha stimulates OCTN2 gene expression and carnitine uptake via NF-kappa B in the bovine Madin-Darby bovine kidney (MDBK) cell line. Treatment with TNF alpha caused activation of NF-kappa B, increased the mRNA and protein concentration of OCTN2, and stimulated the uptake of carnitine in MDBK cells. In contrast, combined treatment of MDBK cells with TNF alpha and the NF-kappa B inhibitor BAY 11-7085 completely blocked the effect of TNF alpha on OCTN2 mRNA and protein concentration and uptake of carnitine. These findings suggest that the bovine OCTN2 gene and carnitine uptake are regulated by NF-kappa B. Future studies are required to show the in vivo relevance of this regulatory mechanism in cattle.

Harvard Citation style: Zhou, X., Ringseis, R., Wen, G. and Eder, K. (2015) The pro-inflammatory cytokine tumor necrosis factor alpha stimulates expression of the carnitine transporter OCTN2 (novel organic cation transporter 2) and carnitine uptake via nuclear factor-kappa B in Madin-Darby bovine kidney cells, Journal of Dairy Science, 98(6), pp. 3840-3848. https://doi.org/10.3168/jds.2014-9044

APA Citation style: Zhou, X., Ringseis, R., Wen, G., & Eder, K. (2015). The pro-inflammatory cytokine tumor necrosis factor alpha stimulates expression of the carnitine transporter OCTN2 (novel organic cation transporter 2) and carnitine uptake via nuclear factor-kappa B in Madin-Darby bovine kidney cells. Journal of Dairy Science. 98(6), 3840-3848. https://doi.org/10.3168/jds.2014-9044