Role of the adipocyte-specific NF-κB activity in the regulation of IP-10 and T cell migration

Author:

Krinninger Patricia1,Brunner Cornelia2,Ruiz Pedro A.3,Schneider Elisabeth1,Marx Nikolaus4,Foryst-Ludwig Anna5,Kintscher Ulrich5,Haller Dirk3,Laumen Helmut1,Hauner Hans1

Affiliation:

1. Else Kröner-Fresenius-Centre for Nutritional Medicine,

2. Institute of Physiological Chemistry,

3. Chair for Biofunctionality, Nutrition and Food Research Centre, Technische Universität München, Munich, Germany;

4. Department of Internal Medicine II-Cardiology, University of Ulm, Ulm, Germany; and

5. Center for Cardiovascular Research, Institute of Pharmacology, Charité-Universitätsmedizin Berlin, Germany

Abstract

Infiltration of immune cells into adipose tissue plays a central role in the pathophysiology of obesity-associated low-grade inflammation. The aim of this study was to analyze the role of adipocyte NF-κB signaling in the regulation of the chemokine/adipokine interferon-γ-induced protein 10 kDa (IP-10) and adipocyte-mediated T cell migration. Therefore, the regulation of IP-10 was investigated in adipose tissue of male C57BL/6J mice, primary human and 3T3-L1 preadipocytes/adipocytes. To specifically block the NF-κB pathway, 3T3-L1 cells stably overexpressing a transdominant mutant of IκBα were generated, and the chemical NF-κB inhibitor Bay117082 was used. Adipocyte-mediated T cell migration was assessed by a migration assay. It could be shown that IP-10 expression was higher in mature adipocytes compared with preadipocytes. Induced IP-10 expression and secretion were completely blocked by an NF-κB inhibitor in 3T3-L1 and primary human adipocytes. Stable overexpression of a transdominant mutant of IκBα in 3T3-L1 adipocytes led to an inhibition of basal and stimulated IP-10 expression and secretion. T cell migration was induced by 3T3-L1 adipocyte-conditioned medium, and both basal and induced T cell migration was strongly inhibited by stable overexpression of a transdominant IκBα mutant. In addition, with the use of an anti-IP-10 antibody, a significant decrease of adipocyte-induced T cell migration was shown. In conclusion, in this study, we could demonstrate that the NF-κB pathway is essential for the regulation of IP-10 in 3T3-L1 and primary human adipocytes. Adipocytes rather than preadipocytes contribute to NF-κB-dependent IP-10 expression and secretion. Furthermore, NF-κB-dependent factors and especially IP-10 represent novel signals from adipocytes to induce T cell migration.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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