Negative cross-talk between interleukin-3 and interleukin-11 is mediated by suppressor of cytokine signalling-3 (SOCS-3).
Previous studies have shown that addition of interleukin-3 (IL-3) abrogated the B-cell potential of primary colonies supported by IL-11, erythropoietin, IL-7 and steel factor. However, the mechanism by which IL-3 exerts its inhibitory role is not understood. Using a variant of the mouse pro-B cell line Ba/F3 which expresses both IL-3 and IL-11 receptors, we showed that pretreatment of these cells with IL-3 before stimulation by IL-11 suppressed the tyrosine phosphorylation and nuclear translocation of STAT3 (signal transducer and activator of transcription 3). This inhibition occurred within 30 min and required the synthesis of a negative regulator. The onset of IL-3-dependent inhibition was correlated temporally with the appearance of SOCS-3 (suppressor of cytokine signalling-3) protein. In addition, overexpression of SOCS-3 in the pro-B cell line effectively blocked STAT3 activation induced by IL-11. These findings establish that a cytokine (IL-3) that has been shown to modulate its own signal of activation is also able to down-regulate signalling activated by a different cytokine (IL-11). This cross-talk involves activation of the JAK (Janus kinase)/STAT signalling pathway, but not mitogen-activated protein kinase pathways, and is mediated, at least in part, by SOCS-3.
Magrangeas
F
F
Unité INSERM 463, Institut de Biologie, CHR de Nantes, 9 Quai Moncousu, 44095 Nantes Cedex 01, France.
Boisteau
O
O
Denis
S
S
Jacques
Y
Y
Minvielle
S
S
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017370:Interleukin-11 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007377:Interleukin-3 / Q000737:chemistry / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008894:Milk Proteins; D010766:Phosphorylation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494200:Il6st protein, mouse; D017370:Interleukin-11; D007377:Interleukin-3; D008562:Membrane Glycoproteins; D008894:Milk Proteins; D011506:Proteins; D018123:Receptors, Interleukin; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050822:Cytokine Receptor gp130