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This version published online on August 21, 2003
Endocrinology, doi:10.1210/en.2003-0854
A more recent version of this article appeared on December 1, 2003
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Submitted on July 10, 2003
Accepted on August 12, 2003

In vitro and in vivo calcitonin-I gene expression in parenchymal cells: a novel product of human adipose tissue

Philippe Linscheid1*, Dalma Seboek1, Eric S. Nylen1, Igor Langer1, Mirjam Schlatter1, Ulrich Keller1, Kenneth L. Becker1, and Beat Müller1

1 Department of Research (P.L., D.S.), Division of Endocrinology, Diabetology and Clinical Nutrition (U.K., B.M.), Department of Visceral Surgery (I.L.), and Department of Plastic Surgery (M.S.), University Hospitals, CH-4031 Basel, Switzerland and Dept. of Medicine, George Washington University and Veterans Affairs Medical Center (E.S.N., K.L.B.), Washington, DC 20422

* To whom correspondence should be addressed. E-mail: Philippe.Linscheid{at}unibas.ch.

Circulating levels of calcitonin precursors (CTpr), including procalcitonin (ProCT), increase up to several-thousand-fold in human sepsis and immunoneutralization improves survival in two animal models of this disease. Herein, we analyzed inflammation-mediated calcitonin-I gene (CALC I) gene expression in human adipocyte primary cultures and in adipose tissue samples from infected and non-infected patients with different levels of serum ProCT. In ex vivo differentiated adipocytes, expression of CT-mRNA increased 24-fold (P < 0.05) by the administration of Escherichia coli endotoxin (LPS) and 37-fold (P < 0.05) by interleukin-1{beta} (IL-1{beta}) after 6 h. ProCT protein secretion into culture supernatant increased 13.5-fold (P < 0.01) with LPS treatment and 15.2-fold (P < 0.01) by IL-1{beta} after 48 h. In co-culture experiments, adipocyte CT-mRNA expression was evoked by Escherichia coli activated macrophages, in which CT-mRNA was undetectable. The marked IL-1{beta}-mediated-ProCT release was inhibited by 89% during co-administration with interferon-{gamma} (IFN-{gamma}). In patients with infection and markedly increased serum ProCT, CT-mRNA was detected in adipose tissue biopsies. Hence, we demonstrate that ProCT, which is suspected to mediate deleterious effects in sepsis and inflammation, is a novel product of adipose tissue secretion. The inhibiting effect of IFN-{gamma} on IL-1{beta} -induced CT-mRNA expression and on ProCT secretion might explain previous observations that serum ProCT concentrations increase less in systemic viral compared with bacterial infections.


Key words: Adipocytes • calcitonin • procalcitonin • sepsis • interleukin-1{beta} • interferon-{gamma} • endotoxin




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