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Int. J. Mol. Sci. 2017, 18(8), 1672;

The Effects of Selective Hematopoietic Expression of Human IL-37 on Systemic Inflammation and Atherosclerosis in LDLr-Deficient Mice

Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Post Zone C7Q, P.O. Box 9600, 2300 RC Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, P.O. Box 9600, 2300 RC Leiden, The Netherlands
Department of Pulmonology, Leiden University Medical Center, Leiden P.O. Box 9600, 2300 RC Leiden, The Netherlands
Department of General Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, 6525 HP Nijmegen, The Netherlands
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
Division of Human Nutrition, Wageningen University, 6708 PB Wageningen, The Netherlands
Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, 53113 Bonn, Germany
Department of Medicine, University of Colorado, Aurora, CO 80045, USA
These authors contributed equally to this study.
Author to whom correspondence should be addressed.
Received: 29 June 2017 / Revised: 21 July 2017 / Accepted: 28 July 2017 / Published: 9 August 2017
(This article belongs to the Special Issue Natural Anti-Inflammatory Agents)
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The human cytokine interleukin (IL)-37 has potent anti-inflammatory capacities, and hematopoietic cell-specific transgenic overexpression of IL-37 in mice protects against septic shock and colitis. In the present study we investigated the effect of hematopoietic expression of IL-37 on atherosclerosis development under low-grade inflammatory conditions. Low-density lipoprotein receptor (LDLr)-deficient mice were lethally irradiated and transplanted with bone marrow from IL-37-transgenic or control wild-type mice and fed a Western-type diet (WTD; 1% cholesterol) for eight weeks. Metabolic and inflammatory parameters were monitored and atherosclerosis was assessed in the aortic valve area. Hematopoietic IL-37 expression did not influence body weight, food intake and plasma cholesterol levels during the study. Plasma soluble E-selectin levels were increased with WTD-feeding as compared to chow-feeding, but were not influenced by IL-37 expression. IL-37 expression reduced the inflammatory state as indicated by reduced white blood cell counts and by reduced basal and lipopolysaccharide-induced cytokine response by peritoneal macrophages ex vivo. IL-37 expression did not influence the atherosclerotic lesion area. Lesion composition was marginally affected. Smooth muscle cell content was decreased, but macrophage and collagen content were not different. We conclude that under low-grade inflammatory conditions, hematopoietic IL-37 expression reduces the inflammatory state, but does not influence atherosclerosis development in hyperlipidemic LDLr-deficient mice. View Full-Text
Keywords: atherosclerosis; inflammation; interleukin-37; hyperlipidemia atherosclerosis; inflammation; interleukin-37; hyperlipidemia

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Hoeke, G.; Khedoe, P.P.S.; Van Diepen, J.A.; Pike-Overzet, K.; Van de Ven, B.; Vazirpanah, N.; Mol, I.; Hiemstra, P.S.; Staal, F.J.; Stienstra, R.; Netea, M.G.; Dinarello, C.A.; Rensen, P.C.; Berbée, J.F. The Effects of Selective Hematopoietic Expression of Human IL-37 on Systemic Inflammation and Atherosclerosis in LDLr-Deficient Mice. Int. J. Mol. Sci. 2017, 18, 1672.

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