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.

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. © 2018 American Chemical Society.

Citation

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. https://doi.org/10.1021/acs.jproteome.7b00828

• 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
• DOI: https://doi.org/10.1021/acs.jproteome.7b00828
• 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
• Public URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045030888&doi=10.1021%2facs.jproteome.7b00828&partnerID=40&md5=64606905acf0b95c7f9c2684003e3e76
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.jproteome.7b00828