Suppression of chronic damage in renal allografts by liver X receptor (LXR) activation

• Verfasst von: Kiss, Eva [VerfasserIn]
• Verfasst von: Popovic, Zoran V. [VerfasserIn]
• Verfasst von: Bedke, Jens [VerfasserIn]
• Verfasst von: Wang, Shijun [VerfasserIn]
• Verfasst von: Bonrouhi, Mahnaz [VerfasserIn]
• Verfasst von: Gretz, Norbert [VerfasserIn]
• Verfasst von: Stettner, Paula [VerfasserIn]
• Verfasst von: Teupser, Daniel [VerfasserIn]
• Verfasst von: Thiery, Joachim [VerfasserIn]
• Verfasst von: Porubský, Štefan [VerfasserIn]
• Verfasst von: Adams, Judith [VerfasserIn]
• Verfasst von: Gröne, Hermann-Josef [VerfasserIn]
• Titel: Suppression of chronic damage in renal allografts by liver X receptor (LXR) activation
• Titelzusatz: relevant contribution of macrophage LXRα
• Verf.angabe: Eva Kiss, Zoran Popovic, Jens Bedke, Shijun Wang, Mahnaz Bonrouhi, Norbert Gretz, Paula Stettner, Daniel Teupser, Joachim Thiery, Stefan Porubsky, Judith Adams, and Hermann-Josef Gröne
• E-Jahr: 2011
• Jahr: 5 May 2011
• Umfang: 12 S.
• Fussnoten: Gesehen am 04.08.2022
• Titel Quelle: Enthalten in: The American journal of pathology
• Ort Quelle: New York [u.a.] : Elsevier, 1925
• Jahr Quelle: 2011
• Band/Heft Quelle: 179(2011), 1, Seite 92-103
• ISSN Quelle: 1525-2191
• DOI: doi:10.1016/j.ajpath.2011.03.019
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1813239800

Abstract

Liver X receptors (LXR)-α,β regulate intracellular cholesterol homeostasis and inhibit inflammatory gene expression. We studied the effects of the LXRα,β-agonist GW3965 on acute and chronic organ damage in the F344-LEW rat kidney transplantation model. In addition, to gain LXR isoform and cell-specific insights BALB/c kidneys were transplanted into mice with macrophage overexpression of LXRα (mLXRα-tg) and evaluated 7 and 42 days after transplantation. After 56 days GW3965 improved significantly function and morphology of rat kidney allografts by substantial reduction of mononuclear cell infiltrate and fibrosis; in vitro GW3965 reduced inflammatory activity of bone marrow-derived macrophages (BMDMs) and alloreactivity of T cells. Kidneys transplanted into mLXRα-tg mice were also protected from development of chronic allograft dysfunction. Similarly to GW3965-activated BMDMs, mLXRα-tg macrophages secreted significantly less monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β. Interestingly, 7 days after transplantation, when the total number of intragraft macrophages did not differ, evidently more arginase 1- and mannose receptor C type 1-positive cells were found in LXR rat and mice kidney allografts; in vitro both LXR activation by GW3965 and mLXRα overexpression accentuated the induction of alternative activation of BMDMs by IL-4/IL-13, suggesting an additional mechanism by LXRs to prevent graft damage. The results highlight the relevance of macrophage LXRα in allograft rejection and prevention of fibrosis.