title: Cytokines as molecular targets for aryl hydrocarbon receptor ligands: implications for toxicity and xenobiotic detoxification.
abstract: BACKGROUND
  The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for regulating expression of several important drug-detoxifying proteins. Besides drug metabolism pathways, cytokines have been recently recognized as targeted by the AhR signaling cascade, which may contribute to toxicity and changes in xenobiotic detoxification caused by AhR agonists.
  
  
  METHODS
  This article summarizes the nature of the main cytokines regulated by AhR ligands and reviews their involvement in toxic effects of AhR ligands, especially in relation with inflammation. The article also discusses the potential implications for drug detoxification pathways.
  
  
  CONCLUSIONS
  Even if various cytokines, including inflammatory ones, have already been demonstrated to constitute robust targets for AhR, the exact role played by AhR with respect to inflammation remains to be determined. Further studies are also required to better characterize the molecular mechanisms implicated in regulation of cytokines by AhR ligands and to determine the role that may play AhR-targeted cytokines in alteration of xenobiotic detoxification. Finally, changes in cytokine receptor expression triggered by AhR ligands have additionally to be taken into account to better and more extensively comprehend the role played by AhR in the cytokine/inflammation area.
authors.affiliation: Institut de Recherche en Environnement, Santé et Travail (IRSET)/INSERM U 1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 35043 Rennes, France. olivier.fardel@univ-rennes1.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Fardel
mesh_terms: D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics