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LPS and Poly I:C Induce Chromatin Modifications at a Novel Upstream Region of the IL-23 p19 Promoter

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Abstract

IL-23, a heterodimer of IL-12 p40 and IL-23 p19, is critical for an effective immune response to many infections and has been implicated in several autoimmune diseases, however, little is known about the regulation of IL-23 gene expression in monocytes. We found that poly I:C, LPS, flagellin, and zymogen activated significant IL-23 production in primary human monocytes. Using chromatin immunoprecipitation, we found that a distal upstream region of the IL-23 p19 promoter at −601 to −521 underwent extensive histone modifications in response to stimuli. This distal region of the promoter is not highly conserved between species and has not been previously implicated in the regulation of IL-23 expression. Knockdown of CBP markedly decreased IL-23 p19 responses to poly I:C but had a less dramatic effect on LPS responses, confirming different chromatin responses to these two stimuli. Our data suggest that one of the mechanisms regulating IL-23 expression is the regulation of histone modifications at this distal upstream region of the promoter.

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Acknowledgements

This work was supported by NIH grants AI051323 and AI44127. The authors wish to acknowledge the Human Immunology Core at the University of Pennsylvania, which provided the primary monocytes for this study. Stacey Garrett was supported in part by The University of Pennsylvania School of Medicine Cancer Research Institute Predoctoral Emphasis on Pathways in Tumor Immunology Training Grant.

Authors’ Contributions

SG carried out the ChIP studies and drafted the manuscript. MF performed the knockdown and the RT-PCR experiments. KS provided oversight of the study design and final wording of the text. All authors read and approved the final manuscript.

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  1. The Division of Allergy and Immunology, The Children’s Hospital of Philadelphia, ARC 1216, 34th St. and Civic Ctr. Blvd., Philadelphia, PA, 19104, USA

    Stacey Garrett, Michael C. Fitzgerald & Kathleen E. Sullivan

  2. The Division of Allergy and Immunology, The Children’s Hospital of Philadelphia, ARC 1216, 34th St. and Civic Ctr. Blvd., Philadelphia, PA, 19104, USA

    Kathleen E. Sullivan

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Garrett, S., Fitzgerald, M.C. & Sullivan, K.E. LPS and Poly I:C Induce Chromatin Modifications at a Novel Upstream Region of the IL-23 p19 Promoter. Inflammation 31, 235–246 (2008). https://doi.org/10.1007/s10753-008-9070-6

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