Serum Amyloid A Is an Endogenous Ligand That Differentially Induces IL-12 and IL-23.
The acute-phase proteins, C-reactive protein and serum amyloid A ( SAA), are biomarkers of infection and inflammation. However, their precise role in immunity and inflammation remains undefined. We report in this study a novel property of SAA in the differential induction of Th1-type immunomodulatory cytokines IL-12 and IL-23. In peripheral blood monocytes and the THP-1 monocytic cell line, SAA induces the expression of IL-12p40, a subunit shared by IL-12 and IL-23. SAA-stimulated expression of IL-12p40 was rapid (</=4 h), sustainable (>/=20 h), potent (up to 3380 pg/ml/10(6) cells in 24 h), and insensitive to polymyxin B treatment. The SAA- stimulated IL-12p40 secretion required de novo protein synthesis and was accompanied by activation of the transcription factors NF-kappaB and C/ EBP. Expression of IL-12p40 required activation of the p38 MAPK and PI3K. Interestingly, the SAA-induced IL-12p40 production was accompanied by a sustained expression of IL-23p19, but not IL-12p35, resulting in preferential secretion of IL-23, but not IL-12. These results identify SAA as an endogenous ligand that potentially activates the IL-23/IL-17 pathway and present a novel mechanism for regulation of inflammation and immunity by an acute-phase protein.[1]References
- Serum Amyloid A Is an Endogenous Ligand That Differentially Induces IL-12 and IL-23. He, R., Shepard, L.W., Chen, J., Pan, Z.K., Ye, R.D. J. Immunol. (2006) [Pubmed]
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