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Repression of PPARγ reduces the ABCG2-mediated efflux activity of M2 macrophages

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Abstract
Even though subclasses of macrophage have distinct roles during progression of infectious diseases, it remains poorly understood whether there is a subset-specific difference in drug responses. Here, we report that ABCG2 was expressed specifically in M2-like macrophages and that it controlled their efflux activities. Abcg2 expression is markedly induced during polarization of PMA-primed macrophages toward an M2 type. IL-4 and IL-13 induced Pparg expression through STAT6 and PPARγ in turn acted on the Abcg2 promoter for its transcription activation. Once polarized to M2-like macrophages, these cells had sustained PPARγ transcription activation of Abcg2 gene. Accordingly, interruption of this machinery by T0070907, an inverse agonist of PPARγ, was shown to be effective in Abcg2 downregulation and its efflux activity in M2-like macrophages. Taken together, our results implicate that ABCG2 of M2 macrophages may function as an important pump that plays a potential role in drug efflux and that T0070907 may be used to increase the efficacy of M2 macrophage-targeting drugs such as antibiotics.
Author(s)
김채은박하영윤해정김민영권병석이수진김동현신재국서수길
Issued Date
2021
Type
Article
Keyword
MacrophagesAbcg2Il-4Stat6Ppar
DOI
10.1016/j.biocel.2020.105895
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7691
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2466293725&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Repression%20of%20PPAR%CE%B3%20reduces%20the%20ABCG2-mediated%20efflux%20activity%20of%20M2%20macrophages&offset=0&pcAvailability=true
Publisher
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Location
영국
Language
영어
ISSN
1357-2725
Citation Volume
130
Citation Number
1
Citation Start Page
105895
Citation End Page
105895
Appears in Collections:
Medicine > Medicine
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