Interleukin 9 induces expression of three cytokine signal inhibitors: cytokine-inducible SH2-containing protein, suppressor of cytokine signalling (SOCS)-2 and SOCS-3, but only SOCS-3 overexpression suppresses interleukin 9 signalling
D. Lejeune et al., Interleukin 9 induces expression of three cytokine signal inhibitors: cytokine-inducible SH2-containing protein, suppressor of cytokine signalling (SOCS)-2 and SOCS-3, but only SOCS-3 overexpression suppresses interleukin 9 signalling, BIOCHEM J, 353, 2001, pp. 109-116
Interleukin 9 (IL-9) is a cytokine preferentially produced by T helper type
2 lymphocytes and active on various cell types such as T- and B-lymphocyte
s, mast cells and haemopoietic propenitors, The IL-9 receptor (IL-9R) belon
gs to the haemopoietic receptor superfamily and its signal transduction inv
olves mainly the Janus kinase/signal transducer and activator of transcript
ion (JAK/STAT) pathway. Here we studied the implication of a novel family o
f suppressors of cytokine signalling (called CIS, for cytokine-inducible SH
2-containing protein, and SOCS, for suppressor of cytokine signalling) in I
L-9 signal attenuation. In BW5147 T-cell lymphoma, IL-9 induced the rapid e
xpression of CIS, SOCS-2 and SOCS-3 with a peak after 2 h of stimulation. U
sing IL-9R mutants, we showed that STAT activation is required for CIS/SOCS
induction: CIS and SOCS-2 expression was induced either via STAT1 and/or S
TAT3 or via STAT5 but only STAT1 and/or STAT3 were involved in SOCS-3 expre
ssion. The effect of these three proteins on IL-9 signal transduction was a
ssessed by transient transfection in HEK-293 cells expressing the component
s of the IL-9 signalling pathway and a STAT-responsive reporter construct.
These experiments showed that only SOCS-3 is able to inhibit IL-9-induced s
ignal transduction; neither CIS nor SOCS-2 exerted any effect. Stable trans
fection of CIS and SOCS-3 in BW5147 lymphoma cells showed that only overexp
ression of SOCS-3 had an inhibitory activity on STAT activation, gene induc
tion and the anti-apoptotic activity of IL-9. By contrast, CIS failed to af
fect the IL-9 response.