ARS | Publication request: Association of tumor necrosis factor-alpha(TNF-alpha)gene promoter polymorphisms with TNF-alpha response to endotoxin (LPS)in calves.

Submitted to: Joint Abstracts of the American Dairy Science and Society of Animal Science
Publication Type: Abstract Only
Publication Acceptance Date: March 9, 2008
Publication Date: July 11, 2008
Citation: Kahl, S., Proszkowiec Wegla, M.K., Connor, E.E., Elsasser, T.H. 2008. Association of tumor necrosis factor-alpha(TNF-alpha)gene promoter polymorphisms with TNF-alpha response to endotoxin (LPS)in calves. Joint Abstracts of the American Dairy Science and Society of Animal Science. Journal of Animal Science. Abstract. 86:195.

Technical Abstract: Attenuation of TNF-alpha gene expression is a NF-'B-mediated regulatory process essential to avoid deleterious effects of excessive or prolonged synthesis of TNF-alpha, especially in response to gram-negative bacterial infection or LPS. An uncommon G to A transition polymorphism in the promoter region of TNF-alpha gene (designated the TNF-alpha2 allele) was shown to be highly associated with excessive TNF-alpha production and TNF-alpha-mediated pathologies in humans. We performed a preliminary survey to determine if similar polymorphisms exist in Angus × Hereford calves that might suggest a potential for particular animals to have excessive TNF-alpha responses to LPS challenges. A 574-bp TNF-alpha gene promoter fragment was generated by PCR from bovine genomic DNA and evaluated by bi-directional automated fluorescent sequencing. Two linked single nucleotide polymorphisms were located between NF-'B binding sites at positions -701 (C/T) and -526 (A/G). Calves (n=17; 279 ± 10 kg) were assigned to groups by genotype (4 TT-AA, 5 CT-AG, 8 CC-GG), fed a TMR diet (15% CP) to appetite, and challenged with two consecutive LPS injections 4 d apart (LPS1, LPS2; 0.2 µg E. coli 055:B5/kg BW, i.v.). Jugular blood samples were obtained at 0, 1, 2, and 4 h relative to each LPS injection. Plasma TNF-alpha was measured by RIA and TNF-alpha response was calculated as area under the time × concentration curve (AUC; ng/mL x h). After LPS1, mean TNF-a responses were greater in TT-AA than CT-AG and CC-GG calves (4.9, 2.2, and 3.0, respectively; P < 0.05). While for each calf the TNF-alpha response to LPS2 was numerically lower than that calculated for LPS1 (indicating LPS tolerance attenuation was achieved), mean TNF-alpha responses to LPS2 were still greater in TT-AA than CT-AG and CC-GG calves (3.3, 1.0, and 1.1, respectively; P < 0.01). The magnitude of the attenuation was less in TT-AA than in CC-GG calves (P < 0.05). The results suggest that polymorphisms in the TNF-alpha gene promoter may play a role in the intensity of the TNF-alpha response to proinflammatory stimuli in cattle.