IFN-beta stimulates the production of beta-chemokines in human peripheral blood monocytes. Importance of macrophage differentiation.
We investigated the effect of IFN-beta on beta-chemokine expression in differentiating human peripheral blood monocytes. MCP-1, MIP-1alpha and MIP-1beta were constitutively expressed in 1 day-cultured monocytes, and their secretion increased with time in culture despite any change in mRNA accumulation. IFN-beta treatment of differentiating monocytes resulted in a marked and dose-dependent increase of beta-chemokine secretion, which was regulated differently with respect to the differentiation stage. In particular, IFN-beta upregulated MCP-1 secretion in monocytes at all stages of differentiation although its effect was significantly higher in 1-day cultured monocytes as compared to monocyte-derived macrophages (MDM). In contrast, MIP-1alpha and MIP-1beta secretion was up-regulated by IFN-beta only in MDM. Although MCP-1, MIP-1alpha and MIP-1beta mRNA expression was up-regulated by IFN-beta in both 1 day-cultured monocytes and MDM, no correlation was found between mRNA level and protein secretion. These results suggest that the regulation of beta-chemokine secretion in monocytes/macrophages by IFN-beta occurred through different mechanisms, involving both a direct effect of this cytokine on chemokine gene expression and translational/post-translational steps of regulation more likely linked to the differentiation process. This finding reveals a novel role for this cytokine in the recruitment of specific cell types during the immune response, which may be relevant in the control of viral infections in vivo.
Fantuzzi
L
L
Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Canini
I
I
Belardelli
F
F
Gessani
S
S
D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000502:physiology*; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000502:physiology*; D008264:Macrophages / Q000166:cytology*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics
D019742:Chemokines, CC; D012333:RNA, Messenger; D016899:Interferon-beta