International Immunology Advance Access originally published online on April 18, 2005
International Immunology 2005 17(5):649-659; doi:10.1093/intimm/dxh247
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IL-12 family members: differential kinetics of their TLR4-mediated induction by Salmonella Enteritidis and the impact of IL-10 in bone marrow-derived macrophages
1 Institute of Immunology, College of Veterinary Medicine and Biotechnological-Biomedical Center (BBZ), University of Leipzig, An den Tierkliniken 11, 04103 Leipzig, Germany
2 Max Planck Institute of Immunobiology, Research Group for Medical Microbiology, Stübeweg 51, 79011 Freiburg, Germany
Correspondence to: R. K. Straubinger; E-mail: straubinger{at}uni-leipzig.de
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 BMDM
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 BMDM. 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.
Keywords: bacteria, cytokine, LPS, mouse, pattern recognition receptor
Transmitting editor: G. Trinchieri
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