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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.


Cheng Huang

Caitlin Lewis

Natalie A. Borg

Henry Diep

Grant R. Drummond

Robert J. Goode

Ralf B. Schittenhelm

Antony Vinh

Mingyu Zhu

Barbara Kemp-Harper

Oded Kleifeld

Martin J. Stone


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. © 2018 American Chemical Society.


Huang, C., Lewis, C., Borg, N. A., Canals, M., Diep, H., Drummond, G. R., …Stone, M. J. (2018). Proteomic Identification of Interferon-Induced Proteins with Tetratricopeptide Repeats as Markers of M1 Macrophage Polarization. Journal of Proteome Research, 17(4), 1485-1499.

Journal Article Type Article
Acceptance Date Mar 5, 2018
Online Publication Date Mar 6, 2018
Publication Date Apr 6, 2018
Deposit Date Jan 17, 2020
Journal Journal of Proteome Research
Print ISSN 1535-3893
Electronic ISSN 1535-3907
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 17
Issue 4
Pages 1485-1499
Keywords biological marker; interferon regulatory factor 1; messenger RNA; transcription factor AP 1; animal experiment; animal model; animal tissue; aortic sinus; Article; atherosclerosis; brachiocephalic trunk; cell isolation; cell polarity; human; human cell; h
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