PMID- 29719531 OWN - NLM STAT- MEDLINE DCOM- 20190625 LR - 20240314 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 9 DP - 2018 TI - Characterization of Chicken Tumor Necrosis Factor-alpha, a Long Missed Cytokine in Birds. PG - 605 LID - 10.3389/fimmu.2018.00605 [doi] LID - 605 AB - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine playing critical roles in host defense and acute and chronic inflammation. It has been described in fish, amphibians, and mammals but was considered to be absent in the avian genomes. Here, we report on the identification and functional characterization of the avian ortholog. The chicken TNF-alpha (chTNF-alpha) is encoded by a highly GC-rich gene, whose product shares with its mammalian counterpart 45% homology in the extracellular part displaying the characteristic TNF homology domain. Orthologs of chTNF-alpha were identified in the genomes of 12 additional avian species including Palaeognathae and Neognathae, and the synteny of the closely adjacent loci with mammalian TNF-alpha orthologs was demonstrated in the crow (Corvus cornix) genome. In addition to chTNF-alpha, we obtained full sequences for homologs of TNF-alpha receptors 1 and 2 (TNFR1, TNFR2). chTNF-alpha mRNA is strongly induced by lipopolysaccharide (LPS) stimulation of monocyte derived, splenic and bone marrow macrophages, and significantly upregulated in splenic tissue in response to i.v. LPS treatment. Activation of T-lymphocytes by TCR crosslinking induces chTNF-alpha expression in CD4(+) but not in CD8(+) cells. To gain insights into its biological activity, we generated recombinant chTNF-alpha in eukaryotic and prokaryotic expression systems. Both, the full-length cytokine and the extracellular domain rapidly induced an NFkappaB-luciferase reporter in stably transfected CEC-32 reporter cells. Collectively, these data provide strong evidence for the existence of a fully functional TNF-alpha/TNF-alpha receptor system in birds thus filling a gap in our understanding of the evolution of cytokine systems. FAU - Rohde, Franziska AU - Rohde F AD - Department of Veterinary Science, Ludwig-Maximilians-Universitat, Munich, Germany. FAU - Schusser, Benjamin AU - Schusser B AD - Reproductive Biotechnology, Department of Animal Sciences, Technical University Munich, Munich, Germany. FAU - Hron, Tomas AU - Hron T AD - Laboratory of Viral and Cellular Genetics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia. FAU - Farkasova, Helena AU - Farkasova H AD - Laboratory of Viral and Cellular Genetics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia. FAU - Plachy, Jiri AU - Plachy J AD - Laboratory of Viral and Cellular Genetics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia. FAU - Hartle, Sonja AU - Hartle S AD - Department of Veterinary Science, Ludwig-Maximilians-Universitat, Munich, Germany. FAU - Hejnar, Jiri AU - Hejnar J AD - Laboratory of Viral and Cellular Genetics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia. FAU - Elleder, Daniel AU - Elleder D AD - Laboratory of Viral and Cellular Genetics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia. FAU - Kaspers, Bernd AU - Kaspers B AD - Department of Veterinary Science, Ludwig-Maximilians-Universitat, Munich, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180417 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Avian Proteins) RN - 0 (NF-kappa B) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Avian Proteins/*genetics/metabolism MH - CD4-Positive T-Lymphocytes/*immunology MH - Cells, Cultured MH - Chickens/*immunology MH - Cloning, Molecular MH - Crows/immunology MH - GC Rich Sequence/genetics MH - Humans MH - Macrophages/*immunology MH - Mammals/immunology MH - NF-kappa B/metabolism MH - Palaeognathae/immunology MH - Receptors, Tumor Necrosis Factor/*genetics/metabolism MH - Sequence Alignment MH - Tumor Necrosis Factor-alpha/*genetics PMC - PMC5913325 OTO - NOTNLM OT - avian OT - biological activity OT - chicken OT - missing gene OT - tumor necrosis factor-alpha OT - tumor necrosis factor-alpha receptors EDAT- 2018/05/03 06:00 MHDA- 2018/05/03 06:01 PMCR- 2018/01/01 CRDT- 2018/05/03 06:00 PHST- 2017/12/05 00:00 [received] PHST- 2018/03/09 00:00 [accepted] PHST- 2018/05/03 06:00 [entrez] PHST- 2018/05/03 06:00 [pubmed] PHST- 2018/05/03 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2018.00605 [doi] PST - epublish SO - Front Immunol. 2018 Apr 17;9:605. doi: 10.3389/fimmu.2018.00605. eCollection 2018.