Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State
Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1) or anti-inflammatory (M2). Paraoxonase 2 (PON2) is expressed in macrophages, and it...
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| Format: | Article |
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Wiley
2015-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2015/915243 |
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| author | Marie Koren-Gluzer Mira Rosenblat Tony Hayek |
| author_facet | Marie Koren-Gluzer Mira Rosenblat Tony Hayek |
| author_sort | Marie Koren-Gluzer |
| collection | DOAJ |
| description | Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1) or anti-inflammatory (M2). Paraoxonase 2 (PON2) is expressed in macrophages, and it was shown to protect against atherosclerosis. Thus, the aim of our study was to analyze the direct effect of PON2 on macrophage inflammatory phenotypes. Ex vivo studies were performed with murine peritoneal macrophages (MPM) harvested from control C57BL/6 and PON2-deficient (PON2KO) mice. PON2KO MPM showed an enhanced proinflammatory phenotype compared to the control, both in the basal state and following M1 activation by IFNγ and lipopolysaccharide (LPS). In parallel, PON2KO MPM also showed reduced anti-inflammatory responses in the basal state and also following M2 activation by IL-4. Moreover, the PON2-null MPM demonstrated enhanced phagocytosis and reactive oxygen species (ROS) production in the basal state and following M1 activation. The direct effect of PON2 was shown by transfecting human PON2 (hPON2) into PON2KO MPM. PON2 transfection attenuated the macrophages’ response to M1 activation and enhanced M2 response. These PON2 effects were associated with attenuation of macrophages’ abilities to phagocyte and to generate ROS. We conclude that PON2 promotes an M1 to M2 switch in macrophage phenotypes. |
| format | Article |
| id | doaj-art-8ab209fe0277420c97cfb19b1144681b |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
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| series | International Journal of Endocrinology |
| spelling | doaj-art-8ab209fe0277420c97cfb19b1144681b2025-02-03T06:08:10ZengWileyInternational Journal of Endocrinology1687-83371687-83452015-01-01201510.1155/2015/915243915243Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory StateMarie Koren-Gluzer0Mira Rosenblat1Tony Hayek2The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, and Rambam Health Care Campus, 31096 Haifa, IsraelThe Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, and Rambam Health Care Campus, 31096 Haifa, IsraelThe Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, and Rambam Health Care Campus, 31096 Haifa, IsraelInflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1) or anti-inflammatory (M2). Paraoxonase 2 (PON2) is expressed in macrophages, and it was shown to protect against atherosclerosis. Thus, the aim of our study was to analyze the direct effect of PON2 on macrophage inflammatory phenotypes. Ex vivo studies were performed with murine peritoneal macrophages (MPM) harvested from control C57BL/6 and PON2-deficient (PON2KO) mice. PON2KO MPM showed an enhanced proinflammatory phenotype compared to the control, both in the basal state and following M1 activation by IFNγ and lipopolysaccharide (LPS). In parallel, PON2KO MPM also showed reduced anti-inflammatory responses in the basal state and also following M2 activation by IL-4. Moreover, the PON2-null MPM demonstrated enhanced phagocytosis and reactive oxygen species (ROS) production in the basal state and following M1 activation. The direct effect of PON2 was shown by transfecting human PON2 (hPON2) into PON2KO MPM. PON2 transfection attenuated the macrophages’ response to M1 activation and enhanced M2 response. These PON2 effects were associated with attenuation of macrophages’ abilities to phagocyte and to generate ROS. We conclude that PON2 promotes an M1 to M2 switch in macrophage phenotypes.http://dx.doi.org/10.1155/2015/915243 |
| spellingShingle | Marie Koren-Gluzer Mira Rosenblat Tony Hayek Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State International Journal of Endocrinology |
| title | Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State |
| title_full | Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State |
| title_fullStr | Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State |
| title_full_unstemmed | Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State |
| title_short | Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State |
| title_sort | paraoxonase 2 induces a phenotypic switch in macrophage polarization favoring an m2 anti inflammatory state |
| url | http://dx.doi.org/10.1155/2015/915243 |
| work_keys_str_mv | AT mariekorengluzer paraoxonase2inducesaphenotypicswitchinmacrophagepolarizationfavoringanm2antiinflammatorystate AT mirarosenblat paraoxonase2inducesaphenotypicswitchinmacrophagepolarizationfavoringanm2antiinflammatorystate AT tonyhayek paraoxonase2inducesaphenotypicswitchinmacrophagepolarizationfavoringanm2antiinflammatorystate |