In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue.
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) expression in human adipocyte primary cultures and in adipose tissue samples from infected and noninfected patients with different levels of serum ProCT. In ex vivo differentiated adipocytes, the expression of CT mRNA increased 24-fold (P < 0.05) after the administration of Escherichia coli endotoxin (lipopolysaccharide) and 37-fold (P < 0.05) after IL-1beta administration by 6 h. ProCT protein secretion into culture supernatant increased 13.5-fold (P < 0.01) with lipopolysaccharide treatment and 15.2-fold (P < 0.01) with IL-1beta after 48 h. In coculture experiments, adipocyte CT mRNA expression was evoked by E. coli-activated macrophages in which CT mRNA was undetectable. The marked IL-1beta-mediated ProCT release was inhibited by 89% during coadministration with interferon-gamma (IFNgamma). 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 IFNgamma on IL-1beta-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.
Linscheid
Philippe
P
Department of Research, University Hospitals, Hebelstrasse 20, 4031 Basel, Switzerland. philippe.linscheid@unibas.ch.
Seboek
Dalma
D
Nylen
Eric S
ES
Langer
Igor
I
Schlatter
Mirjam
M
Becker
Kenneth L
KL
Keller
Ulrich
U
Müller
Beat
B
D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology*; D002116:Calcitonin / Q000235:genetics*; D015740:Calcitonin Gene-Related Peptide; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D009852:Omentum / Q000503:physiopathology; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018805:Sepsis / Q000503:physiopathology*
C000606589:CALCA protein, human; D011498:Protein Precursors; D012333:RNA, Messenger; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide