The search for sensitive and specific markers of systemic infection has shown that procalcitonin levels are increased in sepsis, and, consequently, this plasma protein has come into the focus of clinical research. Human procalcitonin is encoded by the Calc-l gene, which gives rise to two alternatively spliced transcripts. Despite systemic investigation of the Calc-l gene and mechanisms of the tissue-specific regulation and alternative splicing, little is known about the biology of procalcitonin and the cells which express this protein during inflammation. Here we focus on the molecular and biochemical properties of the molecule and summarize the known biological functions of procalcitonin. We report on the structure of the Calc-l gene, the amino acid conservation of procalcitonin in different species, and the consensus sequences of the protein with regard to sites relevant for posttranslational modification, spatial distribution, and homologies to other cytokines. We discuss aspects of intracellular location of procalcitonin and demonstrate that it has the characteristics of a secreted protein.

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Heme oxygenase-1 (HO-1) is the inducible form of the rate-limiting enzyme of heme degradation; it regulates the cellular content of heme. To investigate the role of the cAMP-dependent protein kinase (PKA) signaling pathway on hepatic HO-1 gene expression, primary rat hepatocyte cultures were treated with the PKA-stimulating agents dibutyryl-cAMP (Bt2cAMP), forskolin, and glucagon. HO-1 mRNA levels were induced by these agents in a time-dependent manner with a transient maximum after 6 hr of treatment. The induction of HO-1 was dose dependent, reaching a maximum at concentrations of 250 muM Bt2cAMP and 50 nM glucagon, respectively. The accumulation of HO-1 mRNA correlated with increased levels of HO-1 protein as determined by Western blot analysis. The Bt2cAMP-dependent induction of HO-1 mRNA expression was prevented by pretreatment with the PKA inhibitor KT5720 but not with the protein kinase G inhibitor KT5823. HO-1 mRNA induction by CdCl2 and heme was differentially affected by Bt2cAMP. Up-regulation of the HO-1 gene by Bt2cAMP occurred on the transcriptional level as determined by nuclear run-off assay and blocking of the Bt2cAMP-dependent induction of HO-1 mRNA by actinomycin D. Treatment with Bt2cAMP increased the half-life of HO-1 mRNA from 4.7 to 5.5 hr. Taken together, the results of the current study demonstrate that HO-1 gene expression is induced by activation of the cAMP signal transduction pathway via a transcriptional mechanism in primary rat hepatocyte cultures.

Treatment of rat hepatocytes with the filamentous-actin-stabilizing toxin phalloidin decreased the amount of globular actin by 77% in the cytosol and by 80% in the nucleus within 12 h. Simultaneously, actin mRNA was specifically increased by 230%. The de-novo synthesis of actin mRNA, as measured by nuclear run-on transcription, was enhanced by 250%. Treatment of cells with actinomycin D blocked the increase of actin mRNA. The apparent half-life of actin mRNA was not significantly altered during treatment with phalloidin.In contrast, the globular-actin-stabilizing botulinum C2 toxin increased the amount of cytosolic globular actin by 50% within 12 h. Simultaneously, the actin mRNA level was decreased by 62%. However, de-novo synthesis of actin mRNA was not impaired. The apparent half-life of actin mRNA was decreased by approximately 60 % during treatment with C2 toxin.The data strongly suggest an autoregulatory control of actin synthesis on the basis of the globular/ filamentous actin ratio in rat hepatocytes at the transcriptional as well as at the posttranscriptional levels.