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ÀúÀÚ¸í Kim CE, Park HY, Won HJ, Kim MY, Kwon BS, Lee SJ, Kim DH, Shin JG, Seo SK
ÇÐȸÁ¤º¸ Int J Biochem Cell Biol. 130:105895 / 2021.01
Á¦ ¸ñ Repression of PPAR¥ã reduces the ABCG2-mediated efflux activity of M2 macrophages
LINK www.ncbi.nlm.nih.gov/pubmed/33259947/
°Ô½ÃÀÏ 2025-03-25 12:08:53
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³»¿ë 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 PPAR¥ã in turn acted on the Abcg2 promoter for its transcription activation. Once polarized to M2-like macrophages, these cells had sustained PPAR¥ã transcription activation of Abcg2 gene. Accordingly, interruption of this machinery by T0070907, an inverse agonist of PPAR¥ã, 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.

Keywords: ABCG2; IL-4; Macrophages; PPAR; STAT6.