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Role of chicken TL1A on inflammatory responses and partial characterization of its receptor

Tetsuya Takimoto1, Kan Sato, Yukio Akiba

  • 1Laboratory of Animal Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.

Journal of Immunology (Baltimore, Md. : 1950)
|June 5, 2008
PubMed

Insights

Chicken TNF-like ligand 1A (ChTL1A) acts as a proinflammatory cytokine, influencing inflammation by binding to TNFR2. This cytokine plays a key role in the chicken immune response, especially after LPS stimulation.

Area of Science:

  • Immunology
  • Cytokine Research
  • Avian Biology

Background:

  • Chickens lack orthologous genes for TNF-alpha and lymphotoxin alpha.
  • Understanding chicken-specific inflammatory mediators is crucial for avian health.
  • Chicken TNF-like ligand 1A (ChTL1A) was hypothesized to be a proinflammatory cytokine.

Purpose of the Study:

  • To investigate the role of ChTL1A in chicken inflammation.
  • To identify receptor candidates for ChTL1A.
  • To elucidate the mechanism of ChTL1A's proinflammatory action.

Main Methods:

  • Cell viability assays using CHO-K1 cells transfected with chicken TNFR2 or decoy receptor 3.
  • Detection of ChTL1A in chicken blood post-LPS injection.
  • mRNA analysis of inflammatory factors in spleen tissue.
  • Measurement of acute phase proteins (ceruloplasmin, alpha(1) acid glycoprotein) and nitrite/nitrate in plasma.
  • In vivo studies using anti-ChTL1A antibody.

Main Results:

  • ChTL1A reduced viability of cells expressing chicken TNFR2 or decoy receptor 3, indicating binding.
  • ChTL1A was detected in blood 4 hours after LPS injection.
  • LPS injection increased mRNA for IL-1beta, IL-6, ChTL1A, IFN-gamma, iNOS, and COX-2 in spleen.
  • ChTL1A injection elevated plasma levels of ceruloplasmin and alpha(1) acid glycoprotein.
  • Anti-ChTL1A antibody administration blocked LPS-induced increases in inflammatory markers.

Conclusions:

  • ChTL1A functions as a proinflammatory cytokine in chickens.
  • Its proinflammatory effects are mediated, at least partly, through binding to chicken TNFR2.
  • ChTL1A is a significant component of the inflammatory response in avian species lacking TNF-alpha and LT-alpha.

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