Serum amyloid A is an endogenous ligand that differentially induces IL-12 and IL-23

Rong He, Larry W. Shepard, Jia Chen, Zhixing K. Pan, Richard D. Ye*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

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 Jh), sustainable (≥20 h), potent (up to 3380 pg/ml/106 cells in 24 h), and insensitive to polymyxin E treatment. The SAA-stimulaled IL-12p40 secretion required de novo protein synthesis and was accompanied by activation of the transcription factors NF-κB 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.

Original languageEnglish (US)
Pages (from-to)4072-4079
Number of pages8
JournalJournal of Immunology
Volume177
Issue number6
DOIs
StatePublished - Sep 15 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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