@article{WollbornWunderStixetal.2015,
  author    = {Wollborn, Jakob and Wunder, Christian and Stix, Jana and Neuhaus, Winfried and Bruno, Rapahel R. and Baar, Wolfgang and Flemming, Sven and Roewer, Norbert and Schlegel, Nicolas and Schick, Martin A.},
  title     = {Phosphodiesterase-4 inhibition with rolipram attenuates hepatocellular injury in hyperinflammation in vivo and in vitro without influencing inflammation and HO-1 expression},
  series = {Journal of Pharmacology and Pharmacotherapeutics},
  volume    = {6},
  journal   = {Journal of Pharmacology and Pharmacotherapeutics},
  number    = {1},
  doi       = {10.4103/0976-500X.149138},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149336},
  pages     = {13-23},
  year      = {2015},
  abstract  = {Objective: To investigate the impact of the phophodiesterase-4 inhibition (PD-4-I) with rolipram on hepatic integrity in lipopolysaccharide (LPS) induced hyperinflammation. Materials and Methods: Liver microcirculation in rats was obtained using intravital microscopy. Macrohemodynamic parameters, blood assays, and organs were harvested to determine organ function and injury. Hyperinflammation was induced by LPS and PD-4-I rolipram was administered intravenously one hour after LPS application. Cell viability of HepG2 cells was measured by EZ4U-kit based on the dye XTT. Experiments were carried out assessing the influence of different concentrations of tumor necrosis factor alpha (TNF-α) and LPS with or without PD-4-I. Results: Untreated LPS-induced rats showed significantly decreased liver microcirculation and increased hepatic cell death, whereas LPS + PD-4-I treatment could improve hepatic volumetric flow and cell death to control level whithout influencing the inflammatory impact. In HepG2 cells TNF-α and LPS significantly reduced cell viability. Coincubation with PD-4-I increased HepG2 viability to control levels. The heme oxygenase 1 (HO-1) pathway did not induce the protective effect of PD-4-I. Conclusion: Intravenous PD-4-I treatment was effective in improving hepatic microcirculation and hepatic integrity, while it had a direct protective effect on HepG2 viability during inflammation.},
  language  = {en}
}
@article{SchickSchlegel2022,
  author    = {Schick, Martin Alexander and Schlegel, Nicolas},
  title     = {Clinical implication of phosphodiesterase-4-inhibition},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {3},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23031209},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284511},
  year      = {2022},
  abstract  = {The pleiotropic function of 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent pathways in health and disease led to the development of pharmacological phosphodiesterase inhibitors (PDE-I) to attenuate cAMP degradation. While there are many isotypes of PDE, a predominant role of PDE4 is to regulate fundamental functions, including endothelial and epithelial barrier stability, modulation of inflammatory responses and cognitive and/or mood functions. This makes the use of PDE4-I an interesting tool for various therapeutic approaches. However, due to the presence of PDE4 in many tissues, there is a significant danger for serious side effects. Based on this, the aim of this review is to provide a comprehensive overview of the approaches and effects of PDE4-I for different therapeutic applications. In summary, despite many obstacles to use of PDE4-I for different therapeutic approaches, the current data warrant future research to utilize the therapeutic potential of phosphodiesterase 4 inhibition.},
  language  = {en}
}