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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1022.)
© 2006 American Heart Association, Inc.

Vascular Biology

LXR Activation Reduces Proinflammatory Cytokine Expression in Human CD4-Positive Lymphocytes

Daniel Walcher; Andreas Kümmel; Bettina Kehrle; Helga Bach; Miriam Grüb; Renate Durst; Vinzenz Hombach; Nikolaus Marx

From the Department of Internal Medicine II, Cardiology, University of Ulm, Germany.

Correspondence to Nikolaus Marx, MD, Department of Internal Medicine II–Cardiology, University of Ulm, Robert-Koch-Str. 8, D-89081 Ulm, Germany. E-mail nikolaus.marx{at}medizin.uni-ulm.de

Background— CD4-positive lymphocytes, the major T-cell population in human atheroma, mainly secrete Th-1-type proinflammatory cytokines, like interferon (IFN), tumor necrosis factor (TNF), and interleukin (IL)-2, thus promoting atherogenesis. Recent data suggest that the nuclear transcription factors liver X receptor-alpha and liver X receptor-beta (LXR and LXRß) limit plaque formation in animal models by modulating macrophage function. Still, the role of LXRs in CD4-positive lymphocytes is currently unexplored.

Methods and Results— Human CD4-positive lymphocytes express LXR and LXRß mRNA and protein. Activation of CD4-positive cells by anti-CD3 mAbs, anti-CD3/CD28 mAbs, as well as PMA/ionomycin significantly increased Th1-cytokine mRNA and protein expression. Treatment with the LXR activator T0901317 reduced this increase of IFN, TNF, and IL-2 in a concentration-dependent manner with a maximum at 1 µmol/L T0901317. Transient transfection assays revealed an inhibition of IFN promoter activity by T0901317 as the underlying molecular mechanism. Such anti-inflammatory actions were also evident in cell–cell interactions with medium conditioned by T0901317-treated CD4-positive cells attenuating human monocyte CD64 expression.

Conclusions— Human CD4-positive lymphocytes express both LXR and LXRß, and LXR activation can reduce Th-1 cytokine expression in these cells. These data provide new insight how LXR activators might modulate the inflammatory process in atherogenesis and as such influence lesion development.

The present study demonstrates both LXR and LXRß expression in human CD4-positive lymphocytes, as well as reduced Th-1 cytokine expression by LXR activation in these cells. These data provide new insight how LXR activators might modulate the inflammatory process in atherogenesis and as such influence lesion development.

Key Words: atherosclerosis • IFN • LXR • T-lymphocytes

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