Role of calcium in lipopolysaccharide-induced calcitonin gene expression in human adipocytes.

Abstract

Severe systemic infections induce ubiquitous calcitonin (CALC) gene expression with release of calcitonin peptides, namely procalcitonin, calcitonin gene-related peptide and adrenomedullin. Using an in vitro model for bacterial infection, we tested the hypothesis that intracellular calcium concentration ([Ca(2+)](i)) is elevated after lipopolysaccharide (LPS) stimulation and is responsible for the LPS-mediated increase in CALC gene expression and protein secretion. In our human adipocyte model, LPS did not show any cytotoxic effects and induced increased CALC-I gene mRNA expression. Additionally, LPS provoked an elevation in [Ca(2+)](i). The LPS-induced increase in CALC-I gene mRNA was partially blocked with verapamil, an L-type calcium channel blocker and blocked almost completely with 2-aminoethoxydiphenyl borate, a blocker of store-operated calcium entry and inositol triphosphate-mediated calcium release. Treatment of cells with substances elevating [Ca(2+)]( i) led to an increased CALC-I mRNA expression level. The combination of LPS with substances raising [Ca(2+)](i) even potentiated this increase. At the same time, elevated [Ca(2+)](i) attenuated the expression level of the CALC-V gene. These findings indicate that, in human adipocytes, changes in [Ca(2+)](i) are involved in LPSregulated expression of CALC genes, thereby strengthening previous findings postulating a crucial role of intracellular calcium homeostasis in the state of bacterial infection and sepsis.

DOI: 10.1177/1753425910377100

Cite this paper

@article{Radimerski2011RoleOC, title={Role of calcium in lipopolysaccharide-induced calcitonin gene expression in human adipocytes.}, author={Tanja M Radimerski and Jean Grisouard and Katharina Timper and Henryk Zulewski and Mirjam Christ-Crain and Ulrich Keller and Beat Mueller}, journal={Innate immunity}, year={2011}, volume={17 4}, pages={403-13} }