Document Detail

Role of the adipocyte-specific NF-{kappa}B activity in the regulation of IP-10 and T cell migration.
MedLine Citation:
PMID:  21062959     Owner:  NLM     Status:  In-Data-Review    
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.
Patricia Krinninger; Cornelia Brunner; Pedro A Ruiz; Elisabeth Schneider; Nikolaus Marx; Anna Foryst-Ludwig; Ulrich Kintscher; Dirk Haller; Helmut Laumen; Hans Hauner
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Publication Detail:
Type:  Journal Article     Date:  2010-11-09
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  300     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E304-11     Citation Subset:  IM    
Else Kröner-Fresenius-Centre for Nutritional Medicine, Gregor-Mendel-Str. 2, 85350 Freising, Germany.
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