{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:06:20Z","timestamp":1779512780498,"version":"3.53.1"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thematic Excellence Programme of the National Research, Development and Innovation Fund, Ministry of Culture and Innovation of Hungary.","award":["TKP2021-EGA-17"],"award-info":[{"award-number":["TKP2021-EGA-17"]}]},{"name":"J\u00e1nos Bolyai Research Scholarship (Hungarian Academy of Sciences).","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Macrophage migration inhibitory factor (MIF) has been shown to induce M1 macrophage polarization with oxidative stress and associated metabolic reprogramming. Several tautomerase inhibitors were shown to selectively inhibit either MIF\u2019s ketonase or enolase sub-activities. In this study, we aimed to investigate the role of enolase sub-activity in M1 polarization using the selective enolase inhibitor TE-91. We performed in silico molecular docking analysis and physicochemical characterization of TE-91. LPS + IFN-\u03b3-induced RAW264.7 cells were applied as a model for M1 macrophage activation. We performed ROS and nitrite determinations, ELISA, qPCR, and immunoblot analysis, and measured mitochondrial oxygen consumption rate and extracellular acidification rate. Here, we reveal that TE-91 might directly bind to the MIF tautomerase active site. Furthermore, TE-91 reduces M1 activation by enhancing oxidative phosphorylation and reducing the glycolytic activity in LPS + IFN-\u03b3-induced macrophage cells. In the same model, TE-91 reduces TNF-\u03b1, IL-6, CCL2, and iNOS mRNA transcription yet fails to modulate PARP1 and SOD2 mRNA transcription. It also decreases ROS, nitrite, and IL-6 production without influencing TNF-\u03b1 and CCL2 protein production. TE-91 was unable to reduce either HIF-1\u03b1 mRNA transcription or its protein expression. Finally, TE-91 reduced IL-1\u03b2 cleavage, without affecting IL-1\u03b2 protein expression. These results may highlight the importance of tautomerase sub-activities in M1 polarization.<\/jats:p>","DOI":"10.3390\/antiox15050640","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:02:27Z","timestamp":1779375747000},"page":"640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Selective MIF Enolase Inhibitor TE-91 Regulates M1 Polarization and Associated Metabolic Reprogramming"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7725-9103","authenticated-orcid":false,"given":"P\u00e9ter","family":"De\u00e1k","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of P\u00e9cs, Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6827-9894","authenticated-orcid":false,"given":"Nikoletta","family":"K\u00e1lm\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of P\u00e9cs, Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7880-8153","authenticated-orcid":false,"given":"Csenge","family":"Antus","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of P\u00e9cs, Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4898-884X","authenticated-orcid":false,"given":"Eva M.","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, A-8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcell","family":"Krek\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Semmelweis University, H-1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-442X","authenticated-orcid":false,"given":"Eszter","family":"V\u00e1mos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of P\u00e9cs, Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7557-3004","authenticated-orcid":false,"given":"Viola Bag\u00f3n\u00e9","family":"V\u00e1ntus","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of P\u00e9cs, Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2143-2009","authenticated-orcid":false,"given":"Katalin","family":"B\u00f6ddi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of P\u00e9cs, Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9764-4763","authenticated-orcid":false,"given":"Lilla","family":"Makszin","sequence":"additional","affiliation":[{"name":"Institute of Bioanalysis, University of P\u00e9cs, Medical School, Szent\u00e1gothai Research Center, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0599-0758","authenticated-orcid":false,"given":"Tam\u00e1s","family":"L\u00f3r\u00e1nd","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of P\u00e9cs, Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1906-4333","authenticated-orcid":false,"suffix":"Jr.","given":"Ferenc","family":"Gallyas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of P\u00e9cs, Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7147-0080","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Radnai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of P\u00e9cs, Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1002\/jcp.26429","article-title":"Macrophage Plasticity, Polarization, and Function in Health and Disease","volume":"233","author":"Mohammadian","year":"2018","journal-title":"J. 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