Engagement of CD11b and CD11c β2 integrin by antibodies or soluble CD23 induces IL-1β production on primary human monocytes through mitogen-activated protein kinase–dependent pathways
| Autor: | Roger Rezzonico, Véronique Imbert, R Chicheportiche, Jean-Michel Dayer |
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| Rok vydání: | 2000 |
| Předmět: | |
| Zdroj: | Blood. 95:3868-3877 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v95.12.3868.012k43_3868_3877 |
| Popis: | beta2 integrins are involved in the recruitment of leukocytes to inflammatory sites and in cellular activation. We demonstrate that ligation of CD11b (Mac-1, CR3) or CD11c (p150, CR4) alpha chains of beta2 integrins by mAbs or soluble chimeric CD23 (sCD23) on human freshly isolated monocytes rapidly stimulates high levels of interleukin-1beta production. This induction takes place at the transcriptional level and is regulated by members of the mitogen-activated protein kinase (MAPK) family. Indeed, stimulation of monocytes through engagement of CD11b or CD11c results in the phosphorylation and activation of ERK1, ERK2, and p38/SAPK2 MAP kinases. U0126, a potent inhibitor of the upstream activator of ERK1/2, ie, MEK1/2, suppresses IL-1beta messenger RNA (mRNA) expression in a dose-dependent fashion, showing the implication of this pathway in the transcriptional control of IL-1beta production. On the other hand, inhibition of p38 by SB203580 indicates that this MAPK is involved in the control of IL-1beta production at both transcriptional and translational levels. Together these data demonstrate that ligation of CD11b and CD11c beta2 integrins by mAbs or sCD23 fusion proteins triggers the activation of 2 distinct MAPK signaling pathways that cooperate in controlling IL-1beta synthesis at different levels. (Blood. 2000;95:3868-3877) |
| Databáze: | OpenAIRE |
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