Role of calcium in lipopolysaccharide-induced calcitonin gene expression in human adipocytes.
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.
Radimerski
Tanja M
TM
Department of Biomedicine, University Hospital Basel, Basel, Switzerland. tanja.radimerski@unibas.ch
Grisouard
Jean
J
Timper
Katharina
K
Zulewski
Henryk
H
Christ-Crain
Mirjam
M
Keller
Ulrich
U
Müller
Beat
B
D017667:Adipocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism*; D001896:Boron Compounds / Q000494:pharmacology; D002116:Calcitonin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000276:immunology / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D001896:Boron Compounds; D002121:Calcium Channel Blockers; D008070:Lipopolysaccharides; D002116:Calcitonin; D014700:Verapamil; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium