title: A tumour necrosis factor alpha autocrine loop contributes to proliferation and nuclear factor-kappaB activation of Theileria parva-transformed B cells.
abstract: Theileria infection of bovine leucocytes induces uncontrolled proliferation and a transformed phenotype comparable to tumour cells. Infected cells have many characteristics of activated leucocytes and use autocrine loops to augment proliferation. We have shown previously that, in infected B cells, PI3-K controls a granulocyte-macrophage colony-stimulating factor (GM-CSF) autocrine loop to increase both proliferation and activation of the activator protein 1 (AP-1) transcription factor. We show here that the same infected B cells also use a tumour necrosis factor (TNF) alpha autocrine loop that again contributes to proliferation and augments nuclear factor (NF)-kappaB activation. Interestingly, both pharmacological inhibition of TNF synthesis and neutralizing anti-TNF antibodies lead to a reduction in proliferation and a 50% drop in NF-kappaB activation, without inducing apoptosis.
authors.affiliation: Laboratoire de Signalisation Immunoparasitaire, URA CNRS 1960, Département de Parasitologie, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Guergnon
authors.forename: Marie
authors.initials: M
authors.lastname: Chaussepied
authors.forename: Paul
authors.initials: P
authors.lastname: Sopp
authors.forename: Regina
authors.initials: R
authors.lastname: Lizundia
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Moreau
authors.forename: Brigitte
authors.initials: B
authors.lastname: Blumen
authors.forename: Dirk
authors.initials: D
authors.lastname: Werling
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Howard
authors.forename: Gordon
authors.initials: G
authors.lastname: Langsley
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000469:parasitology*; D002417:Cattle; D002455:Cell Division; D020869:Gene Expression Profiling; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism*; D016797:Theileria parva / Q000472:pathogenicity*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha