title: Anti-inflammatory effects of tetradecylthioacetic acid (TTA) in macrophage-like cells from Atlantic salmon (Salmo salar L.).
abstract: BACKGROUND
  Commercial Atlantic salmon is fed diets with high fat levels to promote fast and cost-effective growth. To avoid negative impact of obesity, food additives that stimulate fat metabolism and immune function are of high interest. TTA, tetradecylthioacetic acid, is a synthetic fatty acid that stimulates mitochondrial β-oxidation most likely by activation of peroxysome proliferator-activated receptors (PPARs). PPARs are important transcription factors regulating multiple functions including fat metabolism and immune responses. Atlantic salmon experiments have shown that TTA supplemented diets significantly reduce mortality during natural outbreaks of viral diseases, suggesting a modulatory role of the immune system.
  
  
  RESULTS
  To gain new insights into TTA effects on the Atlantic salmon immune system, a factorial, high-throughput microarray experiment was conducted using a 44K oligo nucleotide salmon microarray SIQ2.0 and the Atlantic salmon macrophage-like cell line ASK. The experiment was used to determine the transcriptional effects of TTA, the effects of TTA in poly(I:C) elicited cells and the effects of pretreating the cells with TTA. The expression patterns revealed that a large proportion of genes regulated by TTA were related to lipid metabolism and increased mitochondrial β-oxidation. In addition we found that for a subset of genes TTA antagonized the transcriptional effects of poly(I:C). This, together with the results from qRT-PCR showing an increased transcription of anti-inflammatory IL10 by TTA, indicates anti-inflammatory effects.
  
  
  CONCLUSIONS
  We demonstrate that TTA has significant effects on macrophage-like salmon cells that are challenged by the artificial dsRNA poly(I:C). The immune stimulatory effect of TTA in macrophages involves increased lipid metabolism and suppressed inflammatory status. Thus, suggesting that TTA directs the macrophage-like cells towards alternative, anti-inflammatory, activation. This has positive implications for TTA as a feed additive.
authors.affiliation: Institute of Animal and Aquaculture Sciences, Norwegian University of Life Sciences, P.O. Box 5003, N-1432 As-UMB, Norway.
authors.forename: Fabian
authors.initials: F
authors.lastname: Grammes
authors.forename: Harald
authors.initials: H
authors.lastname: Takle
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D020317:Salmo salar / Q000276:immunology / Q000378:metabolism*; D013440:Sulfides / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D013440:Sulfides; C062078:1-(carboxymethylthio)tetradecane; D011070:Poly I-C