A genetic and functional analysis of novel chicken interleukin-1 gene family members.
Doctoral thesis, UCL (University College London).
The interleukin-1 gene family in humans comprises eleven members (IL-1F1-F11) that act as either functional agonists or antagonists of inflammation. Prior to this project, only two members of the IL-1 family had been identified and characterized in the chicken. The aim of this project was to identify, clone and characterise novel IL-1 family members in this species. EST sequences representing IL-1F5 (IL-36RN) and the secretory and intracellular structural variants of IL-1 receptor antagonist (IL-1RN) were identified by their similarity with chicken IL-1β. Chicken IL-1RN (chIL-1RN) cDNAs were isolated from LPS-stimulated HD11 cells. Two further putative splice variants (SVs) of both chIL-1RN structural variants were also isolated. Both full length variants of chIL-1RN exhibited biological activity resembling that of their mammalian orthologues. The four SVs, however, were not bioactive. ChIL-1RN was constitutively expressed in lymphoid and non-lymphoid tissues as well as several cell subsets. In response to bacterial and viral infection, chIL-1RN expression was inducible. Chicken IL-36RN was cloned from a liver cDNA. In mammals, this cytokine is an IL-1RL2 receptor antagonist and downregulates LPS-mediated inflammation. IL-1RL2 agonist ligands have not been identified in the chicken; therefore, an alternative bioassay to establish its function was attempted. Using a macrophage cell line, chIL-36RN did not inhibit endotoxin-mediated inflammatory effects. Constitutive IL-36RN expression was found in all tissues and cell subsets examined. In response to viral infection, chIL-36RN expression was significantly downregulated. The eleven human IL-1 genes are encoded at three separate loci. Nine of these genes, including IL-1β, IL-1RN and IL-36RN, are present at a single locus. In the chicken genome, the equivalent locus contains only IL-1β. Neither IL-1RN nor IL-36RN were identifiable anywhere in the chicken genome. Future work will seek to determine the true extent of the repertoire of chicken IL-1 family genes.
|Title:||A genetic and functional analysis of novel chicken interleukin-1 gene family members|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health > Department of Infection and Immunity|
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