{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T12:09:44Z","timestamp":1773403784499,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korea government","doi-asserted-by":"publisher","award":["2018R1A5A2021242"],"award-info":[{"award-number":["2018R1A5A2021242"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korea government","doi-asserted-by":"publisher","award":["2020R1I1A3073778"],"award-info":[{"award-number":["2020R1I1A3073778"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background\/Objectives: Macrophages polarized into M1 and M2 phenotypes differentially regulate immune and drug responses. Despite their distinct functional roles, differences in UDP-glucuronosyltransferase (UGT) expression and enzymatic activity between M1 and M2 macrophages remain poorly understood. This study aimed to characterize differential UGT expression in M1 and M2 macrophages and to elucidate how UGT-mediated prostaglandin E2 (PGE2) glucuronidation modulates macrophage inflammatory responses. Methods: THP-1 cells were chemically differentiated into macrophages (M0) and subsequently polarized into M1 and M2 phenotypes. UGT expression profiles were assessed using RT-PCR, quantitative RT-PCR (qRT-PCR), and Western blot. UGT activity was compared by quantifying glucuronide metabolites derived from UGT-specific substrates using LC-MS\/MS, along with measurement of free PGE2 and PGE2-glucuronide by ELISA. Pro-inflammatory cytokine expression and secretion in M1 macrophages were quantified using qRT-PCR and ELISA. Results: Expression of UGT1A1, UGT1A4, UGT1A5, UGT1A9, and UGT2B7 were markedly higher in M1 compared with M2 macrophages at both the mRNA and protein levels. Enhanced UGT activity in M1 macrophages was reflected by increased formation of estradiol-3-glucuronide and naloxone-3-glucuronide (both p &lt; 0.01) and was attenuated in a concentration-dependent manner by diclofenac. Furthermore, PGE2 glucuronidation was more pronounced in M1 macrophages, and inhibition of UGTs with atazanavir reduced PGE2-glucuronide formation and pro-inflammatory cytokine production, including IL-1\u03b2, IL-6, and TNF-\u03b1. Conclusion: UGT-mediated PGE2 glucuronidation in M1 macrophages contributes to the regulation of pro-inflammatory cytokine production. Collectively, these findings support a role for UGTs as modulators of inflammatory signaling, with differential expression and activity between M1 and M2 macrophages.<\/jats:p>","DOI":"10.3390\/jpm16030160","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:26:38Z","timestamp":1773393998000},"page":"160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Macrophage Inflammatory Responses by UDP-Glucuronosyltransferase-Mediated PGE2 Glucuronidation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5419-2795","authenticated-orcid":false,"given":"Dahye","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee Young","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"},{"name":"Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2749-0014","authenticated-orcid":false,"given":"Sangzin","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"},{"name":"Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Soon","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"},{"name":"Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9807-4064","authenticated-orcid":false,"given":"Dong Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"},{"name":"Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5821-850X","authenticated-orcid":false,"given":"Jae-Gook","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"},{"name":"Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3570-0598","authenticated-orcid":false,"given":"Su-Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"},{"name":"Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Inje University, Busan 47392, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2451139","DOI":"10.1002\/eji.202451139","article-title":"Innate Immunity Champions: The Diverse Functions of Macrophages","volume":"54","author":"Biscu","year":"2024","journal-title":"Eur. 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