@article{HenkelAlfineSainetal.2018,
  author    = {Henkel, Janin and Alfine, Eugenia and Sa{\´i}n, Juliana and J{\"o}hrens, Korinna and Weber, Daniela and Castro, Jos{\´e} Pedro and K{\"o}nig, Jeannette and Stuhlmann, Christin and Vahrenbrink, Madita and Jonas, Wenke and Kleinridders, Andr{\´e} and P{\"u}schel, Gerhard Paul},
  title     = {Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol},
  series = {Nutrients},
  volume    = {10},
  journal   = {Nutrients},
  number    = {9},
  publisher = {Molecular Diversity Preservation International (MDPI)},
  address   = {Basel},
  issn      = {2072-6643},
  doi       = {10.3390/nu10091326},
  pages     = {1 -- 17},
  year      = {2018},
  abstract  = {While the impact of dietary cholesterol on the progression of atherosclerosis has probably been overestimated, increasing evidence suggests that dietary cholesterol might favor the transition from blunt steatosis to non-alcoholic steatohepatitis (NASH), especially in combination with high fat diets. It is poorly understood how cholesterol alone or in combination with other dietary lipid components contributes to the development of lipotoxicity. The current study demonstrated that liver damage caused by dietary cholesterol in mice was strongly enhanced by a high fat diet containing soybean oil-derived ω6-poly-unsaturated fatty acids (ω6-PUFA), but not by a lard-based high fat diet containing mainly saturated fatty acids. In contrast to the lard-based diet the soybean oil-based diet augmented cholesterol accumulation in hepatocytes, presumably by impairing cholesterol-eliminating pathways. The soybean oil-based diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis, and caused a transition from steatosis to NASH, doubling the NASH activity score. Thus, the recommendation to reduce cholesterol intake, in particular in diets rich in ω6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.},
  language  = {en}
}
@article{KrupkovaSadowskaKamedaetal.2018,
  author    = {Krupkova, Olga and Sadowska, Aleksandra and Kameda, Takuya and Hitzl, Wolfgang and Hausmann, Oliver Nic and Klasen, J{\"u}rgen and Wuertz-Kozak, Karin},
  title     = {p38 MaPK Facilitates crosstalk Between endoplasmic reticulum stress and IL-6 release in the intervertebral Disc},
  series = {Frontiers in Immunology},
  volume    = {9},
  journal   = {Frontiers in Immunology},
  publisher = {Frontiers Research Foundation},
  address   = {Lausanne},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2018.01706},
  pages     = {14},
  year      = {2018},
  abstract  = {Degenerative disc disease is associated with increased expression of pro-inflammatory cytokines in the intervertebral disc (IVD). However, it is not completely clear how inflammation arises in the IVD and which cellular compartments are involved in this process. Recently, the endoplasmic reticulum (ER) has emerged as a possible modulator of inflammation in age-related disorders. In addition, ER stress has been associated with the microenvironment of degenerated IVDs. Therefore, the aim of this study was to analyze the effects of ER stress on inflammatory responses in degenerated human IVDs and associated molecular mechanisms. Gene expression of ER stress marker GRP78 and pro-inflammatory cytokines IL-6, IL-8, IL-1 beta, and TNF-alpha was analyzed in human surgical IVD samples (n = 51, Pfirrmann grade 2-5). The expression of GRP78 positively correlated with the degeneration grade in lumbar IVDs and IL-6, but not with IL-1 beta and TNF-alpha. Another set of human surgical IVD samples (n = 25) was used to prepare primary cell cultures. ER stress inducer thapsigargin (Tg, 100 and 500 nM) activated gene and protein expression of IL-6 and induced phosphorylation of p38 MAPK. Both inhibition of p38 MAPK by SB203580 (10 mu M) and knockdown of ER stress effector CCAAT-enhancer-binding protein homologous protein (CHOP) reduced gene and protein expression of IL-6 in Tg-treated cells. Furthermore, the effects of an inflammatory microenvironment on ER stress were tested. TNF-alpha (5 and 10 ng/mL) did not activate ER stress, while IL-1 beta (5 and 10 ng/mL) activated gene and protein expression of GRP78, but did not influence [Ca2+](i) flux and expression of CHOP, indicating that pro-inflammatory cytokines alone may not induce ER stress in vivo. This study showed that IL-6 release in the IVD can be initiated following ER stress and that ER stress mediates IL-6 release through p38 MAPK and CHOP. Therapeutic targeting of ER stress response may reduce the consequences of the harsh microenvironment in degenerated IVD.},
  language  = {en}
}
@article{PloehnEdelmannJaptoketal.2018,
  author    = {Pl{\"o}hn, Svenja and Edelmann, B{\"a}rbel and Japtok, Lukasz and He, Xingxuan and Hose, Matthias and Hansen, Wiebke and Schuchman, Edward H. and Eckstein, Anja and Berchner-Pfannschmidt, Utta},
  title     = {CD40 enhances sphingolipids in orbital fibroblasts},
  series = {Investigative ophthalmology \& visual science},
  volume    = {59},
  journal   = {Investigative ophthalmology \& visual science},
  number    = {13},
  publisher = {Association for Research in Vision and Opthalmology},
  address   = {Rockville},
  issn      = {0146-0404},
  doi       = {10.1167/iovs.18-25466},
  pages     = {5391 -- 5397},
  year      = {2018},
  abstract  = {METHODS. OFs and T cells were derived from GO patients and healthy control (Ctl) persons. S1P abundance in orbital tissues was evaluated by immunofluorescence. OFs were stimulated with CD40 ligand and S1P levels were determined by ELISA. Further, activities of acid sphingomyelinase (ASM), acid ceramidase, and sphingosine kinase were measured by ultraperformance liquid chromatography. Sphingosine and ceramide contents were analyzed by mass spectrometry. Finally, the role for S1P in T-cell attraction was investigated by T-cell migration assays. RESULTS. GO orbital tissue showed elevated amounts of S1P as compared to control samples. Stimulation of CD40 induced S1P expression in GO-derived OFs, while Ctl-OFs remained unaffected. A significant increase of ASM and sphingosine kinase activities, as well as lipid formation, was observed in GO-derived OFs. Migration assay of T cells in the presence of SphK inhibitor revealed that S1P released by GO-OFs attracted T cells for migration. CONCLUSIONS. The results demonstrated that CD40 ligand stimulates GO fibroblast to produce S1P, which is a driving force for T-cell migration. The results support the use of S1P receptor signaling modulators in GO management.},
  language  = {en}
}