A tumour necrosis factor alpha autocrine loop contributes to proliferation and nuclear factor-kappaB activation of Theileria parva-transformed B cells.
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.
Guergnon
Julien
J
Laboratoire de Signalisation Immunoparasitaire, URA CNRS 1960, Département de Parasitologie, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
Chaussepied
Marie
M
Sopp
Paul
P
Lizundia
Regina
R
Moreau
Marie-Françoise
MF
Blumen
Brigitte
B
Werling
Dirk
D
Howard
Christopher J
CJ
Langsley
Gordon
G
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*
D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha