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Role of Chicken TL1A on Inflammatory Responses and Partial Characterization of Its Receptor

Tetsuya Takimoto^*, Kan Sato, Yukio Akiba^* and Kazuaki Takahashi^1,*

^* Laboratory of Animal Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai; and Department of Biological Production, Animal Science, Tokyo University of Agriculture and Technology, Tokyo, Japan

The role of chicken TNF-like ligand 1A (ChTL1A) on inflammation and its receptor candidates was investigated to further understand its function as a proinflammatory cytokine. ChTL1A decreased the viability of CHO-K1 cells transfected with chicken TNFR2 or decoy receptor 3 and bound to TNFR2 and decoy receptor 3. ChTL1A was detected in chicken blood samples taken 4 h after LPS injection. Increased mRNA for inflammatory response-related factors such as IL-1β, IL-6, ChTL1A, IFN-, inducible NO synthase, and cyclooxygenase 2 were found in spleen samples following LPS injection. Ceruloplasmin and ₁ acid glycoprotein (as positive acute phase proteins) were increased in chicken plasma 12 h after ChTL1A injection. The injection of anti-ChTL1A Ab was able to prevent typical increases in plasma nitrite plus nitrate, ceruloplasmin, and ₁ acid glycoprotein concentrations following LPS injection. These results indicate that ChTL1A is a proinflammatory cytokine in chickens, animals that do not have TNF- and lymphotoxin orthologous genes, and that its proinflammatory action is, at least in part, expressed through binding to TNFR2.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Kazuaki Takahashi, 1-1 Tsutsumidori-Amamiyamachi Aoba-ku, Sendai, Japan 981-8555. E-mail address: taka{at}bios.tohoku.ac.jp

² Abbreviations used in this paper: iNOS, inducible NO synthase; AG, acid glycoprotein; Cer, ceruloplasmin; ChTL1A, chicken tumor necrosis factor-like ligand 1A; COX-2, cyclooxygenase 2; DcR, decoy receptor; DR, death receptor; TACE, TNF--converting enzyme; ORF, open reading frame.