Proteomic Identification of Interferon-Induced Proteins with Tetratricopeptide Repeats as Markers of M1 Macrophage Polarization

Cheng Huang, Caitlin Lewis, Natalie A. Borg, Meritxell Canals, Henry Diep, Grant R. Drummond, Robert J. Goode, Ralf B. Schittenhelm, Antony Vinh, Mingyu Zhu, Barbara Kemp-Harper, Oded Kleifeld, Martin J. Stone

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Macrophages, which accumulate in tissues during inflammation, may be polarized toward pro-inflammatory (M1) or tissue reparative (M2) phenotypes. The balance between these phenotypes can have a substantial influence on the outcome of inflammatory diseases such as atherosclerosis. Improved biomarkers of M1 and M2 macrophages would be beneficial for research, diagnosis, and monitoring the effects of trial therapeutics in such diseases. To identify novel biomarkers, we have characterized the global proteomes of THP-1 macrophages polarized to M1 and M2 states in comparison with unpolarized (M0) macrophages. M1 polarization resulted in increased expression of numerous pro-inflammatory proteins including the products of 31 genes under the transcriptional control of interferon regulatory factor 1 (IRF-1). In contrast, M2 polarization identified proteins regulated by components of the transcription factor AP-1. Among the most highly upregulated proteins under M1 conditions were the three interferon-induced proteins with tetratricopeptide repeats (IFITs: IFIT1, IFIT2, and IFIT3), which function in antiviral defense. Moreover, IFIT1, IFIT2, and IFIT3 mRNA were strongly upregulated in M1 polarized human primary macrophages and IFIT1 was also expressed in a subset of macrophages in aortic sinus and brachiocephalic artery sections from atherosclerotic ApoE-/- mice. On the basis of these results, we propose that IFITs may serve as useful markers of atherosclerosis and potentially other inflammatory diseases.

Original languageEnglish
Pages (from-to)1485-1499
Number of pages15
JournalJournal of Proteome Research
Volume17
Issue number4
DOIs
Publication statusPublished - 6 Apr 2018

Keywords

  • macrophage
  • polarization
  • atherosclerosis
  • biomarker
  • proteomics
  • interferon-induced protein with tetratricopeptide repeats
  • IFIT1
  • IFIT2
  • IFIT3
  • interferon-stimulated gene

Cite this

@article{4f7f7ff886a1409f915a2409ca56b0f3,
title = "Proteomic Identification of Interferon-Induced Proteins with Tetratricopeptide Repeats as Markers of M1 Macrophage Polarization",
abstract = "Macrophages, which accumulate in tissues during inflammation, may be polarized toward pro-inflammatory (M1) or tissue reparative (M2) phenotypes. The balance between these phenotypes can have a substantial influence on the outcome of inflammatory diseases such as atherosclerosis. Improved biomarkers of M1 and M2 macrophages would be beneficial for research, diagnosis, and monitoring the effects of trial therapeutics in such diseases. To identify novel biomarkers, we have characterized the global proteomes of THP-1 macrophages polarized to M1 and M2 states in comparison with unpolarized (M0) macrophages. M1 polarization resulted in increased expression of numerous pro-inflammatory proteins including the products of 31 genes under the transcriptional control of interferon regulatory factor 1 (IRF-1). In contrast, M2 polarization identified proteins regulated by components of the transcription factor AP-1. Among the most highly upregulated proteins under M1 conditions were the three interferon-induced proteins with tetratricopeptide repeats (IFITs: IFIT1, IFIT2, and IFIT3), which function in antiviral defense. Moreover, IFIT1, IFIT2, and IFIT3 mRNA were strongly upregulated in M1 polarized human primary macrophages and IFIT1 was also expressed in a subset of macrophages in aortic sinus and brachiocephalic artery sections from atherosclerotic ApoE-/- mice. On the basis of these results, we propose that IFITs may serve as useful markers of atherosclerosis and potentially other inflammatory diseases.",
keywords = "macrophage, polarization, atherosclerosis, biomarker, proteomics, interferon-induced protein with tetratricopeptide repeats, IFIT1, IFIT2, IFIT3, interferon-stimulated gene",
author = "Cheng Huang and Caitlin Lewis and Borg, {Natalie A.} and Meritxell Canals and Henry Diep and Drummond, {Grant R.} and Goode, {Robert J.} and Schittenhelm, {Ralf B.} and Antony Vinh and Mingyu Zhu and Barbara Kemp-Harper and Oded Kleifeld and Stone, {Martin J.}",
year = "2018",
month = "4",
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doi = "10.1021/acs.jproteome.7b00828",
language = "English",
volume = "17",
pages = "1485--1499",
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publisher = "American Chemical Society",
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Proteomic Identification of Interferon-Induced Proteins with Tetratricopeptide Repeats as Markers of M1 Macrophage Polarization. / Huang, Cheng; Lewis, Caitlin; Borg, Natalie A.; Canals, Meritxell; Diep, Henry; Drummond, Grant R.; Goode, Robert J.; Schittenhelm, Ralf B.; Vinh, Antony; Zhu, Mingyu; Kemp-Harper, Barbara; Kleifeld, Oded; Stone, Martin J.

In: Journal of Proteome Research, Vol. 17, No. 4, 06.04.2018, p. 1485-1499.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Proteomic Identification of Interferon-Induced Proteins with Tetratricopeptide Repeats as Markers of M1 Macrophage Polarization

AU - Huang, Cheng

AU - Lewis, Caitlin

AU - Borg, Natalie A.

AU - Canals, Meritxell

AU - Diep, Henry

AU - Drummond, Grant R.

AU - Goode, Robert J.

AU - Schittenhelm, Ralf B.

AU - Vinh, Antony

AU - Zhu, Mingyu

AU - Kemp-Harper, Barbara

AU - Kleifeld, Oded

AU - Stone, Martin J.

PY - 2018/4/6

Y1 - 2018/4/6

N2 - Macrophages, which accumulate in tissues during inflammation, may be polarized toward pro-inflammatory (M1) or tissue reparative (M2) phenotypes. The balance between these phenotypes can have a substantial influence on the outcome of inflammatory diseases such as atherosclerosis. Improved biomarkers of M1 and M2 macrophages would be beneficial for research, diagnosis, and monitoring the effects of trial therapeutics in such diseases. To identify novel biomarkers, we have characterized the global proteomes of THP-1 macrophages polarized to M1 and M2 states in comparison with unpolarized (M0) macrophages. M1 polarization resulted in increased expression of numerous pro-inflammatory proteins including the products of 31 genes under the transcriptional control of interferon regulatory factor 1 (IRF-1). In contrast, M2 polarization identified proteins regulated by components of the transcription factor AP-1. Among the most highly upregulated proteins under M1 conditions were the three interferon-induced proteins with tetratricopeptide repeats (IFITs: IFIT1, IFIT2, and IFIT3), which function in antiviral defense. Moreover, IFIT1, IFIT2, and IFIT3 mRNA were strongly upregulated in M1 polarized human primary macrophages and IFIT1 was also expressed in a subset of macrophages in aortic sinus and brachiocephalic artery sections from atherosclerotic ApoE-/- mice. On the basis of these results, we propose that IFITs may serve as useful markers of atherosclerosis and potentially other inflammatory diseases.

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KW - interferon-induced protein with tetratricopeptide repeats

KW - IFIT1

KW - IFIT2

KW - IFIT3

KW - interferon-stimulated gene

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