title: The functions of the avian receptor activator of NF-κB ligand (RANKL) and its receptors, RANK and osteoprotegerin, are evolutionarily conserved.
abstract: A new member of the chicken TNF superfamily has recently been identified, namely receptor activator of NF-κB ligand (RANKL), as have its signalling receptor, RANK, and its decoy receptor, osteoprotegerin (OPG). In mammals, RANKL and RANK are transmembrane proteins expressed on the surface of Th1 cells and dendritic cells (DC) respectively, whereas OPG is expressed as a soluble protein from osteoblasts and DC. Recombinant soluble chicken RANKL (chRANKL) forms homotrimers whereas chicken OPG (chOPG) forms homodimers, characteristic of these molecules in mammals. ChRANKL, chRANK and chOPG are expressed at the mRNA level in most tissues and organs. ChRANKL is transcriptionally regulated by Ca(2+) mobilisation and enhances the mRNA expression levels of pro-inflammatory cytokines in bone marrow-derived DC (BMDC); this is inhibited by both chOPG-Fc and soluble chRANK-Fc. However, chRANKL does not enhance the expression of cell surface markers in either BMDC or BM-derived macrophages (BMM). Furthermore, chRANKL enhances the survival of APC similar to its mammalian orthologue.
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors: Kate M C
authors: KM
authors: Sutton
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors: Tuanjun
authors: T
authors: Hu
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors: Zhiguang
authors: Z
authors: Wu
authors: CEVA-Phylaxia Veterinary Biologicals Co. Ltd., Szallas u. 5, Budapest H-1107, Hungary.
authors: Botond
authors: B
authors: Siklodi
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. Electronic address: lonneke.vervelde@roslin.ed.ac.uk.
authors: Lonneke
authors: L
authors: Vervelde
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors: Pete
authors: P
authors: Kaiser
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D005075:Biological Evolution; D020013:Calcium Signaling; D002470:Cell Survival; D002645:Chickens / Q000276:immunology*; D017124:Conserved Sequence / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D010006:Osteoblasts / Q000276:immunology*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D030161:Avian Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
keywords: Chicken; Cytokines; DC; Macrophages; Pro-inflammatory; TNF superfamily