In Vitro and in Vivo Calcitonin I Gene Expression in Parenchymal Cells: A Novel Product of Human Adipose Tissue

Abstract

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.

Procalcitonin is more likely to be released by the fetus rather than placental tissue during chorioamnionitis

“…Serial PCT measurements revealed that PCT values were significantly different and varied according to HCA presence or absence. Undetectable PCT values in maternal circulation in combination with positive PCT values in umbilical cord blood as well as the neonatal circulation support the hypothesis that PCT is produced by fetal tissues as a result of the fetal inflammatory response syndrome during chorioamnionitis 16 . There is an apparent gradual rise of PCT in the particular compartments in mother-infant pairs with histological CHA.…”

Acute phase proteins in drain fluid: a new screening tool for colorectal anastomotic leakage? The APPEAL study: analysis of parameters predictive for evident anastomotic leakage

“…15 However, bacterial infection has been shown to induce a release of PCT from different parenchymal tissues and differentiated cell types throughout the body. The serum level of PCT has been suggested to be a sensitive indicator of ongoing abdominal sepsis and could help in deciding whether to perform a relaparotomy.…”

“…12 Procalcitonin (PCT) is a potential marker of acute inflammation that is released from different parenchymal tissues and differentiated cell types throughout the body, mostly from the liver and adipose tissue, in response to interleukin levels increased in case of bacterial infections. [13][14][15][16] The aim of this study is to determine if CRP, LBP, and PCT in drain fluid can serve as noninvasive screening tools for CAL in the early postoperative phase after colorectal surgery.…”

Spielen CRP-Spiegel neben IL-6 und PCT noch eine Rolle für Patienten auf Intensivstationen?/Are circulating levels of CRP compared to IL-6 and PCT still relevant in intensive care unit patients?

“…Das Prohormon PCT wird im Rahmen von systemischen Infektionen durch parenchymale Zellen von Lunge, Leber, Niere, Muskel und Fettgewebe synthetisiert und freigesetzt [6,7] . W ä hrend beim Gesunden nur geringe Konzentrationen von PCT messbar sind [75] , k ö nnen im Fall einer schweren Infektion oder einer Sepsis bis auf das mehrfach Tausendfache erh ö hte Spiegel nachgewiesen werden [8,9] .…”

“…Im Gegensatz zum vollwertigen Hormon spielt PCT f ü r den Calciumhaushalt jedoch keine Rolle. W ä hrend Calcitonin in den C-Zellen der Schilddr ü se synthetisiert wird, induziert eine mikrobielle Infektion die Synthese und Freisetzung von PCT durch parenchymale Zellen, wie zum Beispiel Lunge, Leber, Niere, Muskel und Fettgewebe [6,7] . Die H ö he des Anstiegs korreliert dabei mit dem Schweregrad der Erkrankung und der Prognose [8,9] .…”