Lipopolysaccharide primes neutrophils for a rapid response to IL-10.
Responsiveness of human neutrophils to IL-10 was recently shown to be strictly dependent on the levels of IL-10R1 expression. Activation of signal transducer and activator of transcription 3 (STAT3) phosphorylation and induction of suppressor of cytokine signaling (SOCS)-3 protein by IL-10 are in fact negligible in circulating or freshly isolated ("time 0") neutrophils, but become readily measurable in neutrophils cultured for 4 h in the presence or absence of LPS. In this study, we show that modulation by IL-10 of LPS-induced TNF-alpha, CXCL8/IL-8 and IL-1 receptor antagonist (IL-1ra) mRNA accumulation in neutrophils already expressing a functional IL-10R and antigenic SOCS-3 (i.e. in "4-h-cultured" neutrophils) occurs with kinetics that are similar 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-alpha, CXCL8/IL-8 and IL-1ra mRNA, without any new protein synthesis requirement, if neutrophils have been previously exposed to LPS for at least 4 h. These findings suggest that LPS prepares neutrophils to optimally respond to IL-10 in terms of rapid gene modulation via mechanisms that, presumably, depend on specific LPS-induced protein(s).
Cassatella
Marco A
MA
Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy. marco.cassatella@univr.it
Tamassia
Nicola
N
Crepaldi
Luca
L
McDonald
P P
PP
Ear
Thornin
T
Calzetti
Federica
F
Gasperini
Sara
S
Zanderigo
Floriana
F
Bazzoni
Flavia
F
D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology; D051547:Heme Oxygenase-1; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008565:Membrane Proteins; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D014176:Protein Biosynthesis; D018123:Receptors, Interleukin / Q000502:physiology; D053701:Receptors, Interleukin-10; D012097:Repressor Proteins / Q000502:physiology; D012795:Sialoglycoproteins / Q000235:genetics; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D012795:Sialoglycoproteins; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1