Responsiveness of human neutrophils to IL-10 was recently shown to be strictlydependent on the levels of IL-10R1 expression. Activation of signal transducer andactivator of transcription 3 (STAT3) phosphorylation and induction of suppressor ofcytokine signaling (SOCS)-3 protein by IL-10 are in fact negligible in circulating orfreshly isolated (“time 0”) neutrophils, but become readily measurable in neutrophilscultured for 4 h in the presence or absence of LPS. In this study, we show thatmodulation by IL-10 of LPS-induced TNF-a, CXCL8/IL-8 and IL-1 receptor antagonist(IL-1ra) mRNA accumulation in neutrophils already expressing a functional IL-10R andantigenic SOCS-3 (i.e. in “4-h-cultured” neutrophils) occurs with kinetics that aresimilar to those observed in “time 0” neutrophils, depends on de novo protein synthesis,but does not require SOCS-1, SOCS-3, heme oxygenase and Bcl-3 induction. By contrast,we show that IL-10 alone rapidly modulates the expression of TNF-a, CXCL8/IL-8 andIL-1ra mRNA, without any new protein synthesis requirement, if neutrophils have beenpreviously exposed to LPS for at least 4 h. These findings suggest that LPS preparesneutrophils to optimally respond to IL-10 in terms of rapid gene modulation viamechanisms that, presumably, depend on specific LPS-induced protein(s).

Lipopolysaccharide primes neutrophils for a rapid response to IL-10.

CASSATELLA, Marco Antonio;TAMASSIA, Nicola;CALZETTI, Federica;GASPERINI, Sara;BAZZONI, Flavia
2005

Abstract

Responsiveness of human neutrophils to IL-10 was recently shown to be strictlydependent on the levels of IL-10R1 expression. Activation of signal transducer andactivator of transcription 3 (STAT3) phosphorylation and induction of suppressor ofcytokine signaling (SOCS)-3 protein by IL-10 are in fact negligible in circulating orfreshly isolated (“time 0”) neutrophils, but become readily measurable in neutrophilscultured for 4 h in the presence or absence of LPS. In this study, we show thatmodulation by IL-10 of LPS-induced TNF-a, CXCL8/IL-8 and IL-1 receptor antagonist(IL-1ra) mRNA accumulation in neutrophils already expressing a functional IL-10R andantigenic SOCS-3 (i.e. in “4-h-cultured” neutrophils) occurs with kinetics that aresimilar to those observed in “time 0” neutrophils, depends on de novo protein synthesis,but does not require SOCS-1, SOCS-3, heme oxygenase and Bcl-3 induction. By contrast,we show that IL-10 alone rapidly modulates the expression of TNF-a, CXCL8/IL-8 andIL-1ra mRNA, without any new protein synthesis requirement, if neutrophils have beenpreviously exposed to LPS for at least 4 h. These findings suggest that LPS preparesneutrophils to optimally respond to IL-10 in terms of rapid gene modulation viamechanisms that, presumably, depend on specific LPS-induced protein(s).
neutrophils; IL-10; lipopolysaccharide (LPS); inflammation
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/308695
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