Robust shifts in S100a9 expression with aging: A novel mechanism for chronic inflammation

William R. Swindell; Andrew Johnston; Xianying Xing; Andrew Little; Patrick Robichaud; John J. Voorhees; Gary Fisher; Johann E. Gudjonsson

doi:10.1038/srep01215

Robust shifts in S100a9 expression with aging: A novel mechanism for chronic inflammation

William R. Swindell, Andrew Johnston, Xianying Xing, Andrew Little, Patrick Robichaud, John J. Voorhees, Gary Fisher, Johann E. Gudjonsson

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

Abstract

The S100a8 and S100a9 genes encode a pro-inflammatory protein (calgranulin) that has been implicated in multiple diseases. However, involvement of S100a8/a9 in the basic mechanisms of intrinsic aging has not been established. In this study, we show that shifts in the abundance of S100a8 and S100a9 mRNA are a robust feature of aging in mammalian tissues, involving a range of cell types including the central nervous system. To identify transcription factors that control S100a9 expression, we performed a large-scale transcriptome analysis of 62 mouse and human cell types. We identified cell type-specific trends, as well as robust associations linking S100a9 coexpression to elevated frequency of ETS family motifs, and in particular, to motifs recognized by the transcription factor SPI/PU.1. Sparse occurrence of SATB1 motifs was also a strong predictor of S100a9 coexpression. These findings offer support for a novel mechanism by which a SPI1/PU.1-S100a9 axis sustains chronic inflammation during aging.

Original language	English (US)
Article number	1215
Journal	Scientific reports
Volume	3
DOIs	https://doi.org/10.1038/srep01215
State	Published - 2013
Externally published	Yes

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title = "Robust shifts in S100a9 expression with aging: A novel mechanism for chronic inflammation",

abstract = "The S100a8 and S100a9 genes encode a pro-inflammatory protein (calgranulin) that has been implicated in multiple diseases. However, involvement of S100a8/a9 in the basic mechanisms of intrinsic aging has not been established. In this study, we show that shifts in the abundance of S100a8 and S100a9 mRNA are a robust feature of aging in mammalian tissues, involving a range of cell types including the central nervous system. To identify transcription factors that control S100a9 expression, we performed a large-scale transcriptome analysis of 62 mouse and human cell types. We identified cell type-specific trends, as well as robust associations linking S100a9 coexpression to elevated frequency of ETS family motifs, and in particular, to motifs recognized by the transcription factor SPI/PU.1. Sparse occurrence of SATB1 motifs was also a strong predictor of S100a9 coexpression. These findings offer support for a novel mechanism by which a SPI1/PU.1-S100a9 axis sustains chronic inflammation during aging.",

author = "Swindell, {William R.} and Andrew Johnston and Xianying Xing and Andrew Little and Patrick Robichaud and Voorhees, {John J.} and Gary Fisher and Gudjonsson, {Johann E.}",

note = "Funding Information: This work was supported by the University of Michigan Nathan Shock Center Functional Activity Core (NIH AG013283). Dr. Gudjonsson has received support from the Dermatology Foundation and American Skin Association and is the Frances and Kenneth Eisenberg Emerging Scholar of the Taubman Medical Research Institute (NIH K08AR060802).",

year = "2013",

doi = "10.1038/srep01215",

language = "English (US)",

volume = "3",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

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T1 - Robust shifts in S100a9 expression with aging

T2 - A novel mechanism for chronic inflammation

AU - Swindell, William R.

AU - Johnston, Andrew

AU - Xing, Xianying

AU - Little, Andrew

AU - Robichaud, Patrick

AU - Voorhees, John J.

AU - Fisher, Gary

AU - Gudjonsson, Johann E.

N1 - Funding Information: This work was supported by the University of Michigan Nathan Shock Center Functional Activity Core (NIH AG013283). Dr. Gudjonsson has received support from the Dermatology Foundation and American Skin Association and is the Frances and Kenneth Eisenberg Emerging Scholar of the Taubman Medical Research Institute (NIH K08AR060802).

PY - 2013

Y1 - 2013

N2 - The S100a8 and S100a9 genes encode a pro-inflammatory protein (calgranulin) that has been implicated in multiple diseases. However, involvement of S100a8/a9 in the basic mechanisms of intrinsic aging has not been established. In this study, we show that shifts in the abundance of S100a8 and S100a9 mRNA are a robust feature of aging in mammalian tissues, involving a range of cell types including the central nervous system. To identify transcription factors that control S100a9 expression, we performed a large-scale transcriptome analysis of 62 mouse and human cell types. We identified cell type-specific trends, as well as robust associations linking S100a9 coexpression to elevated frequency of ETS family motifs, and in particular, to motifs recognized by the transcription factor SPI/PU.1. Sparse occurrence of SATB1 motifs was also a strong predictor of S100a9 coexpression. These findings offer support for a novel mechanism by which a SPI1/PU.1-S100a9 axis sustains chronic inflammation during aging.

AB - The S100a8 and S100a9 genes encode a pro-inflammatory protein (calgranulin) that has been implicated in multiple diseases. However, involvement of S100a8/a9 in the basic mechanisms of intrinsic aging has not been established. In this study, we show that shifts in the abundance of S100a8 and S100a9 mRNA are a robust feature of aging in mammalian tissues, involving a range of cell types including the central nervous system. To identify transcription factors that control S100a9 expression, we performed a large-scale transcriptome analysis of 62 mouse and human cell types. We identified cell type-specific trends, as well as robust associations linking S100a9 coexpression to elevated frequency of ETS family motifs, and in particular, to motifs recognized by the transcription factor SPI/PU.1. Sparse occurrence of SATB1 motifs was also a strong predictor of S100a9 coexpression. These findings offer support for a novel mechanism by which a SPI1/PU.1-S100a9 axis sustains chronic inflammation during aging.

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Robust shifts in S100a9 expression with aging: A novel mechanism for chronic inflammation

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