Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?

Sauer, Martin; Doß, Sandra; Ehler, Johannes; Mencke, Thomas; Wagner, Nana-Maria

doi:10.1155/2017/6130725

Cited by 13 publications

(16 citation statements)

References 33 publications

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“…The increase of circulating proinflammatory cytokines in PE can be responsible for the augmentation of systemic PCT levels; furthermore, as we have previously discussed, increased PCT levels induce proinflammatory cytokine production that stimulates PCT release which, in turn, triggers the production of PCT itself, causing a positive loop of PCT secretion [5]. Another role that PCT could play in PE pathogenesis is connected with its cytotoxic activity on hepatocytes and endothelium [39,40]. Indeed, it is well known that peculiar characteristics of PE are endothelial dysfunction and liver damage [70].…”

Section: Review Series: Immunology Of Pregnancymentioning

confidence: 95%

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Overview of procalcitonin in pregnancy and in pre-eclampsia

Mangogna

Agostinis

Ricci

et al. 2019

Clinical and Experimental Immunology

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Procalcitonin (PCT), a precursor for calcitonin, is a prohormone involved in the inflammatory processes, which has been poorly studied in the context of pregnancy. During severe inflammation, PCT derives from almost all cell types, including monocytes and parenchymal tissues, making it a good predictive and diagnostic marker of an inflammatory state with rapidly increased serum levels in inflammation or sepsis. In normal pregnancy, PCT is basally expressed at very low level by decidual cells, even if decidual macrophages, which in normal pregnancy are skewed to M2 macrophages, are resistant to lipopolysaccharide (LPS)-induced production of PCT. As PCT increase is associated with an inflammatory state, several research groups investigated whether PCT can be considered a marker of pre-eclampsia, a pregnancy disease characterized by systemic inflammation. The first aim of this review is to summarize what is already known about the tissues synthesizing PCT, about the stimuli that cause the increase of circulating PCT levels and how PCT acts as a proinflammatory stimulus by itself. Secondly, we will describe the role of this prohormone in normal pregnancy and in pregnancies complicated by pre-eclampsia, highlighting the involvement of the decidual macrophages and the proinflammatory cytokine tumor necrosis factor-α in the modulation of PCT expression in the decidual microenvironment.

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Section: Review Series: Immunology Of Pregnancymentioning

confidence: 95%

“…PCT impair the function and viability of human hepatocytes and endothelium and exert general cytotoxicity in vitro [39,40]. PCT with TNF-α induces endothelial barrier disruption and (at concentrations of 0·02 ng/ml) reduces endothelial cell migration and in-vitro tube formation.…”

Section: Pct Biological Functionsmentioning

confidence: 99%

Overview of procalcitonin in pregnancy and in pre-eclampsia

Mangogna

Agostinis

Ricci

et al. 2019

Clinical and Experimental Immunology

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“…PCT is suspected to be another factor impairing the function of hepatocytes. In the in vitro study on the cell line of human hepatocytes, Sauer et al [21] have demonstrated that PCT directly impairs the function of hepatocytes and exerts cytotoxic effects. Over a period of 72 hours, the hepatocytes were exposed to incremental concentrations of PCT (ranging from 0.01 to 50 ng mL -1 ) or to phosphate-buffered 0.9% NaCl as a negative control and acetaminophen as a positive control.…”

Section: Pct As a Toxic Biomarker Impairing The Function Of Hepatocytmentioning

confidence: 99%

“…The levels of PCT > 50 ng mL -1 affected the proliferation and metabolism of hepatocytes in a similar way as the toxic effects of acetaminophen. The pathomechanism of PCT-induced damage to hepatocytes has not been fully explained and requires further in vivo studies [21].…”

Section: Pct As a Toxic Biomarker Impairing The Function Of Hepatocytmentioning

confidence: 99%

Procalcitonin in liver dysfunction — Dr Jekyll or Mr Hyde?

Woźnica¹,

Łysenko²

2018

Anaesthesiol Intensive Ther

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Serum procalcitonin (PCT) is a sensitive biomarker used for the diagnosis of infection and sepsis. PCT has also some toxic effects. It is not a proinflammatory stimulus, but may augment the inflammatory processes. High levels of PCT in sepsis may lead to hepatocyte necrosis and, as a result, to liver failure. The pathomechanism of the toxic effect of PCT is still unknown. The influence of liver function on PCT levels has not been studied yet. It is not sure whether the liver dysfunction affects the diagnostic and prognostic value of serum PCT levels. In patients with acute liver failure, the usefulness of PCT-level determination remains controversial. Recent studies have shown a potential diagnostic benefit of PCT as a marker of infection in chronic liver diseases. In both groups there is still no consensus on the optimal cut-off value of PCT levels in order to exclude infection. In patients with liver disease, the serum PCT levels should be interpreted with caution, taking into consideration other factors affecting the PCT threshold.

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“…Thus, the liver triggers the inflammatory response of the body in order to eliminate microorganisms efficiently, which represents a double-edged sword that results in liver damage due to an overwhelming systemic inflammatory response [ 5 ]. Liver dysfunction occurs during early sepsis that has been demonstrated at 1.5 h post CLP following mouse surgery [ 6 , 7 ]. This process is an independent factor for multiple organ disorders and sepsis-induced death [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

FC-99 ameliorates sepsis-induced liver dysfunction by modulating monocyte/macrophage differentiation via Let-7a related monocytes apoptosis

et al. 2018

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BackgroundThe liver is a vital target for sepsis-related injury, leading to inflammatory pathogenesis, multiple organ dysfunction and high mortality rates. Monocyte-derived macrophage transformations are key events in hepatic inflammation. N1-[(4-methoxy)methyl]-4-methyl-1,2-benzenediamine (FC-99) previously displayed therapeutic potential on experimental sepsis. However, the underlying mechanism of this protective effect is still not clear.ResultsFC-99 treatment attenuated the liver dysfunction in septic mice that was accompanied with reduced numbers of pro-inflammatory Ly6Chi monocytes in the peripheral blood and CD11b+F4/80lo monocyte-derived macrophages in the liver. These effects were attributed to the FC-99-induced apoptosis of CD11b+ cells. In PMA-differentiated THP-1 cells, FC-99 repressed the expression of CD11b, CD14 and caspase3 and resulted in a high proportion of Annexin V+ cells. Moreover, let-7a-5p expression was abrogated upon CLP stimulation in vivo, whereas it was restored by FC-99 treatment. TargetScan analysis and luciferase assays indicated that the anti-apoptotic protein BCL-XL was targeted by let-7a-5p. BCL-XL was inhibited by FC-99 in order to induce monocyte apoptosis, leading to the impaired monocyte-to-macrophage differentiation.Materials and MethodsMurine acute liver failure was generated by caecal ligation puncture surgery after FC-99 administration; Blood samples and liver tissues were collected to determine the monocyte/macrophage subsets and the induction of apoptosis. Human acute monocytic leukemia cell line (THP-1) cells were pretreated with FC-99 followed by phorbol-12-myristate-13-acetate (PMA) stimulation, in order to induce monocyte-to-macrophage differentiation. The target of FC-99 and the mechanistic analyses were conducted by microarrays, qRT-PCR validation, TargetScan algorithms and a luciferase report assay.ConclusionsFC-99 exhibits potential therapeutic effects on CLP-induced liver dysfunction by restoring let-7a-5p levels.

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Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?

Cited by 13 publications

References 33 publications

Overview of procalcitonin in pregnancy and in pre-eclampsia

Overview of procalcitonin in pregnancy and in pre-eclampsia

Procalcitonin in liver dysfunction — Dr Jekyll or Mr Hyde?

FC-99 ameliorates sepsis-induced liver dysfunction by modulating monocyte/macrophage differentiation via Let-7a related monocytes apoptosis

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