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IL-12 family members: differential kinetics of their TLR-4 mediated induction by Salmonella Enteritidis and the impact of IL-10 in bone marrow-derived macrophages

MPG-Autoren
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Mueller,  Uwe
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Freudenberg,  Marina A.
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Zitation

Schuetze, N., Schoeneberger, S., Mueller, U., Freudenberg, M. A., Alber, G., & Straubinger, R. K. (2005). IL-12 family members: differential kinetics of their TLR-4 mediated induction by Salmonella Enteritidis and the impact of IL-10 in bone marrow-derived macrophages. International Immunology, 17, 649-659.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-002B-93DA-3
Zusammenfassung
The members of the IL-12 family of heterodimeric cytokines play a pivotal role in initiation and regulation of cell-mediated immunity. Best known is IL-12p70, which promotes an immune response towards Th1 bias. Other members of this family (IL-23, IL-27) are less well characterized in terms of induction and function. Using either heat-killed or viable Salmonella Enteritidis or LPS as a stimulus, the kinetics of mRNA production of each member of the IL-12 family (p19, p28, p35, p40, Ebstein-Barr-Virus-induced gene 3 (EBI-3)) were determined in BMDMΦ originating from wild-type, Toll-like receptor (TLR)2- and/or TLR4-deficient mice. It was found that following either type of stimulation, a characteristic mRNA expression pattern was observed for each cytokine subunit. Whereas p19 was induced early and transiently, p40 and p35 were up-regulated later and then continuously, but the secretion of IL-23 and IL-12p70 was significantly reduced by IL-10. The up-regulation of p28 mRNA occurred also delayed and declined afterwards, whereas the initial high-level expression of EBI-3 remained almost unchanged in BMDMΦ. Furthermore, a splice variant of the EBI-3 mRNA was discovered. In this context, the cytokine mRNA up-regulation by whole Salmonella Enteritidis is mediated chiefly by TLR4, but depends on additional pattern recognition receptors other than TLR2 expressed by macrophages.