@article{SzymanskiToenniesBecheretal.2012,
  author    = {Szymanski, Kolja V. and T{\"o}nnies, Mario and Becher, Anne and Fatykhova, Diana and N'Guessan, Philippe D. and Gutbier, Birgitt and Klauschen, Frederick and Neusch{\"a}fer-Rube, Frank and Schneider, Paul and R{\"u}ckert, Jens and Neudecker, Jens and Bauer, Torsten T. and Dalhoff, Klaus and Droemann, Daniel and Gruber, Achim D. and Kershaw, Olivia and Temmesfeld-Wollbrueck, Bettina and Suttorp, Norbert and Hippenstiel, Stefan and Hocke, Andreas C.},
  title     = {Streptococcus pneumoniae-induced regulation of cyclooxygenase-2 in human lung tissue},
  series = {The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology},
  volume    = {40},
  journal   = {The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology},
  number    = {6},
  publisher = {European Respiratory Society},
  address   = {Sheffield},
  issn      = {0903-1936},
  doi       = {10.1183/09031936.00186911},
  pages     = {1458 -- 1467},
  year      = {2012},
  abstract  = {The majority of cases of community-acquired pneumonia are caused by Streptococcus pneumoniae and most studies on pneumococcal host interaction are based on cell culture or animal experiments. Thus, little is known about infections in human lung tissue. Cyclooxygenase-2 and its metabolites play an important regulatory role in lung inflammation. Therefore, we established a pneumococcal infection model on human lung tissue demonstrating mitogen-activated protein kinase (MAPK)-dependent induction of cyclooxygenase-2 and its related metabolites. In addition to alveolar macrophages and the vascular endothelium, cyclooxygenase-2 was upregulated in alveolar type II but not type I epithelial cells, which was confirmed in lungs of patients suffering from acute pneumonia. Moreover, we demonstrated the expression profile of all four E prostanoid receptors at the mRNA level and showed functionality of the E prostanoid(4) receptor by cyclic adenosine monophosphate production. Additionally, in comparison to previous studies, cyclooxygenase-2/prostaglandin E-2 related pro- and anti-inflammatory mediator regulation was partly confirmed in human lung tissue after pneumococcal infection. Overall, cell type-specific and MAPK-dependent cyclooxygenase-2 expression and prostaglandin E-2 formation in human lung tissue may play an important role in the early phase of pneumococcal infections.},
  language  = {en}
}
@phdthesis{Ganesh2013,
  author    = {Ganesh, Bhanu Priya},
  title     = {Host-microbe interactions in the inflamed gut},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-69558},
  school      = {Universit{\"a}t Potsdam},
  year      = {2013},
  abstract  = {Initiation and perpetuation of inflammatory bowel diseases (IBD) may result from an exaggerated mucosal immune response to the luminal microbiota in a susceptible host. We proposed that this may be caused either 1) by an abnormal microbial composition or 2) by weakening of the protective mucus layer due to excessive mucus degradation, which may lead to an easy access of luminal antigens to the host mucosa triggering inflammation. We tested whether the probiotic Enterococcus faecium NCIMB 10415 (NCIMB) is capable of reducing chronic gut inflammation by changing the existing gut microbiota composition and aimed to identify mechanisms that are involved in possible beneficial effects of the probiotic. To identify health-promoting mechanisms of the strain, we used interleukin (IL)-10 deficient mice that spontaneously develop gut inflammation and fed these mice a diet containing NCIMB (106 cells g-1) for 3, 8 and 24 weeks, respectively. Control mice were fed an identically composed diet but without the probiotic strain. No clear-cut differences between the animals were observed in pro-inflammatory cytokine gene expression and in intestinal microbiota composition after probiotic supplementation. However, we observed a low abundance of the mucin-degrading bacterium Akkermansia muciniphila in the mice that were fed NCIMB for 8 weeks. These low cell numbers were associated with significantly lower interferon gamma (IFN-γ) and IFN-γ-inducible protein (IP-10) mRNA levels as compared to the NCIMB-treated mice that were killed after 3 and 24 weeks of intervention. In conclusion, NCIMB was not capable of reducing gut inflammation in the IL-10-/- mouse model. To further identify the exact role of A. muciniphila and uncover a possible interaction between this bacterium, NCIMB and the host in relation to inflammation, we performed in vitro studies using HT-29 colon cancer cells. The HT-29 cells were treated with bacterial conditioned media obtained by growing either A. muciniphila (AM-CM) or NCIMB (NCIMB-CM) or both together (COMB-CM) in Dulbecco's Modified Eagle Medium (DMEM) for 2 h at 37 °C followed by bacterial cell removal. HT-29 cells treated with COMB-CM displayed reduced cell viability after 18 h (p<0.01) and no viable cells were detected after 24 h of treatment, in contrast to the other groups or heated COMB-CM. Detection of activated caspase-3 in COMB-CM treated groups indicated that death of the HT-29 cells was brought about by apoptosis. It was concluded that either NCIMB or A. muciniphila produce a soluble and heat-sensitive factor during their concomitant presence that influences cell viability in an in vitro system. We currently hypothesize that this factor is a protein, which has not yet been identified. Based on the potential effect of A. muciniphila on inflammation (in vivo) and cell-viability (in vitro) in the presence of NCIMB, we investigated how the presence of A. muciniphila affects the severity of an intestinal Salmonella enterica Typhimurium (STm)-induced gut inflammation using gnotobiotic C3H mice with a background microbiota of eight bacterial species (SIHUMI, referred to as simplified human intestinal microbiota). Presence of A. muciniphila in STm-infected SIHUMI (SIHUMI-AS) mice caused significantly increased histopathology scores and elevated mRNA levels of IFN-γ, IP-10, tumor necrosis factor alpha (TNF-α), IL-12, IL-17 and IL-6 in cecal and colonic tissue. The number of mucin filled goblet cells was 2- to 3- fold lower in cecal tissue of SIHUMI-AS mice compared to SIHUMI mice associated with STm (SIHUMI-S) or A. muciniphila (SIHUMI-A) or SIHUMI mice. Reduced goblet cell numbers significantly correlated with increased IFN-γ (r2 = -0.86, ***P<0.001) in all infected mice. In addition, loss of cecal mucin sulphation was observed in SIHUMI-AS mice. Concomitant presence of A. muciniphila and STm resulted in a drastic change in microbiota composition of the SIHUMI consortium. The proportion of Bacteroides thetaiotaomicron in SIHUMI, SIHUMI-A and SIHUMI-S mice made up to 80-90\% but was completely taken over by STm in SIHUMI-AS mice contributing 94\% to total bacteria. These results suggest that A. muciniphila exacerbates STm-induced intestinal inflammation by its ability to disturb host mucus homeostasis. In conclusion, abnormal microbiota composition together with excessive mucus degradation contributes to severe intestinal inflammation in a susceptible host.},
  language  = {en}
}
@article{ManowskyCamargoKippetal.2016,
  author    = {Manowsky, Julia and Camargo, Rodolfo Gonzalez and Kipp, Anna Patricia and Henkel, Janin and P{\"u}schel, Gerhard Paul},
  title     = {Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes},
  series = {American journal of physiology : Endocrinology and metabolism},
  volume    = {310},
  journal   = {American journal of physiology : Endocrinology and metabolism},
  publisher = {American Chemical Society},
  address   = {Bethesda},
  issn      = {0193-1849},
  doi       = {10.1152/ajpendo.00427.2015},
  pages     = {E938 -- E946},
  year      = {2016},
  abstract  = {Overweight and obesity are associated with hyperinsulinemia, insulin resistance, and a low-grade inflammation. Although hyperinsulinemia is generally thought to result from an attempt of the beta-cell to compensate for insulin resistance, there is evidence that hyperinsulinaemia itself may contribute to the development of insulin resistance and possibly the low-grade inflammation. To test this hypothesis, U937 macrophages were exposed to insulin. In these cells, insulin induced expression of the proinflammatory cytokines IL-1 beta, IL-8, CCL2, and OSM. The insulin-elicited induction of IL-1 beta was independent of the presence of endotoxin and most likely mediated by an insulin-dependent activation of NF-kappa B. Supernatants of the insulin-treated U937 macrophages rendered primary cultures of rat hepatocytes insulin resistant; they attenuated the insulin-dependent induction of glucokinase by 50\%. The cytokines contained in the supernatants of insulin-treated U937 macrophages activated ERK1/2 and IKK beta, resulting in an inhibitory serine phosphorylation of the insulin receptor substrate. In addition, STAT3 was activated and SOCS3 induced, further contributing to the interruption of the insulin receptor signal chain in hepatocytes. These results indicate that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues.},
  language  = {en}
}
@phdthesis{Radloff2018,
  author    = {Radloff, Katrin},
  title     = {The role of the fatty acid profile and its modulation by cytokines in the systemic inflammation in cancer cachexia},
  school      = {Universit{\"a}t Potsdam},
  pages     = {156},
  year      = {2018},
  abstract  = {Systemic inflammation is a hallmark of cancer cachexia. Among tumor-host interactions, the white adipose tissue (WAT) is an important contributor to inflammation as it suffers morphological reorganization and lipolysis, releasing free fatty acids (FA), bioactive lipid mediators (LM) and pro-inflammatory cytokines, which accentuate the activation of pro-inflammatory signaling pathways and the recruitment of immune cells to the tissue. This project aimed to investigate which inflammatory factors are involved in the local adipose tissue inflammation and what is the influence of such factors upon enzymes involved in FA or LM metabolism in healthy individuals (Control), weight stable gastro-intestinal cancer patients (WSC) and cachectic cancer patients (CC). The results demonstrated that the inflammatory signature of systemic inflammation is different from local adipose tissue inflammation. The systemic inflammation of the cachectic cancer patients was characterized by higher levels of circulating saturated fatty acids (SFA), tumor-necrosis-factor-α (TNF-α), interleukins IL-6, IL-8 and CRP while levels of polyunsaturated fatty acids (PUFAs), especially n3-PUFAs, were lower in CC than in the other groups. In vitro and in adipose tissue explants, pro-inflammatory cytokines and SFAs were shown to increase the chemokines IL-8 and CXCL10 that were found to be augmented in adipose tissue inflammation in CC which was more profound in the visceral adipose tissue (VAT) than in subcutaneous adipose tissue (SAT). Systemic inflammation was negatively associated with the expression of PUFA synthesizing enzymes, though gene and protein expression did hardly differ between groups. The effects of inflammatory factors on enzymes in the whole tissue could have been masked by differentiated modulation of the diverse cell types in the same tissue. In vitro experiments showed that the expression of FA-modifying enzymes such as desaturases and elongases in adipocytes and macrophages was regulated into opposing directions by TNF-α, IL-6, LPS or palmitate. The higher plasma concentration of the pro-resolving LM resolvin D1 in CC cannot compensate the overall inflammatory status and the results indicate that inflammatory cytokines interfere with synthesis pathways of pro-resolving LM. In summary, the data revealed a complex inter-tissue and inter-cellular crosstalk mediated by pro-inflammatory cytokines and lipid compounds enhancing inflammation in cancer cachexia by feed-forward mechanisms.},
  language  = {en}
}
@misc{HassHerpichNorman2019,
  author    = {Haß, Ulrike and Herpich, Catrin and Norman, Kristina},
  title     = {Anti-Inflammatory Diets and Fatigue},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {803},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-44117},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-441172},
  pages     = {26},
  year      = {2019},
  abstract  = {Accumulating data indicates a link between a pro-inflammatory status and occurrence of chronic disease-related fatigue. The questions are whether the observed inflammatory profile can be (a) improved by anti-inflammatory diets, and (b) if this improvement can in turn be translated into a significant fatigue reduction. The aim of this narrative review was to investigate the effect of anti-inflammatory nutrients, foods, and diets on inflammatory markers and fatigue in various patient populations. Next to observational and epidemiological studies, a total of 21 human trials have been evaluated in this work. Current available research is indicative, rather than evident, regarding the effectiveness of individuals' use of single nutrients with anti-inflammatory and fatigue-reducing effects. In contrast, clinical studies demonstrate that a balanced diet with whole grains high in fibers, polyphenol-rich vegetables, and omega-3 fatty acid-rich foods might be able to improve disease-related fatigue symptoms. Nonetheless, further research is needed to clarify conflicting results in the literature and substantiate the promising results from human trials on fatigue.},
  language  = {en}
}
@article{HassHerpichNorman2019,
  author    = {Haß, Ulrike and Herpich, Catrin and Norman, Kristina},
  title     = {Anti-Inflammatory Diets and Fatigue},
  series = {Nutrients},
  volume    = {11},
  journal   = {Nutrients},
  number    = {10},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2072-6643},
  doi       = {10.3390/nu11102315},
  pages     = {24},
  year      = {2019},
  abstract  = {Accumulating data indicates a link between a pro-inflammatory status and occurrence of chronic disease-related fatigue. The questions are whether the observed inflammatory profile can be (a) improved by anti-inflammatory diets, and (b) if this improvement can in turn be translated into a significant fatigue reduction. The aim of this narrative review was to investigate the effect of anti-inflammatory nutrients, foods, and diets on inflammatory markers and fatigue in various patient populations. Next to observational and epidemiological studies, a total of 21 human trials have been evaluated in this work. Current available research is indicative, rather than evident, regarding the effectiveness of individuals' use of single nutrients with anti-inflammatory and fatigue-reducing effects. In contrast, clinical studies demonstrate that a balanced diet with whole grains high in fibers, polyphenol-rich vegetables, and omega-3 fatty acid-rich foods might be able to improve disease-related fatigue symptoms. Nonetheless, further research is needed to clarify conflicting results in the literature and substantiate the promising results from human trials on fatigue.},
  language  = {en}
}
@misc{ZwaagHorstBlaženovićetal.2020,
  author    = {Zwaag, Jelle and Horst, Rob ter and Blaženović, Ivana and St{\"o}ßel, Daniel and Ratter, Jacqueline and Worseck, Josephine M. and Schauer, Nicolas and Stienstra, Rinke and Netea, Mihai G. and Jahn, Dieter and Pickkers, Peter and Kox, Matthijs},
  title     = {Involvement of lactate and pyruvate in the anti-inflammatory effects exerted by voluntary activation of the sympathetic nervous system},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {4},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-51778},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-517784},
  pages     = {20},
  year      = {2020},
  abstract  = {We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1 beta and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects.},
  language  = {en}
}
@article{ZwaagHorstBlaženovićetal.2020,
  author    = {Zwaag, Jelle and Horst, Rob ter and Blaženović, Ivana and St{\"o}ßel, Daniel and Ratter, Jacqueline and Worseck, Josephine M. and Schauer, Nicolas and Stienstra, Rinke and Netea, Mihai G. and Jahn, Dieter and Pickkers, Peter and Kox, Matthijs},
  title     = {Involvement of lactate and pyruvate in the anti-inflammatory effects exerted by voluntary activation of the sympathetic nervous system},
  series = {Metabolites},
  volume    = {10},
  journal   = {Metabolites},
  number    = {4},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2218-1989},
  doi       = {10.3390/metabo10040148},
  pages     = {1 -- 18},
  year      = {2020},
  abstract  = {We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1 beta and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects.},
  language  = {en}
}
@misc{KesslerHornemannRudovichetal.2020,
  author    = {Kessler, Katharina and Hornemann, Silke and Rudovich, Natalia and Weber, Daniela and Grune, Tilman and Kramer, Achim and Pfeiffer, Andreas F. H. and Pivovarova-Ramich, Olga},
  title     = {Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {2},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-51207},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-512079},
  pages     = {14},
  year      = {2020},
  abstract  = {Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies.},
  language  = {en}
}
@article{KesslerHornemannRudovichetal.2020,
  author    = {Kessler, Katharina and Hornemann, Silke and Rudovich, Natalia and Weber, Daniela and Grune, Tilman and Kramer, Achim and Pfeiffer, Andreas F. H. and Pivovarova-Ramich, Olga},
  title     = {Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers},
  series = {Nutrients},
  journal   = {Nutrients},
  number    = {2},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2072-6643},
  doi       = {10.3390/nu12020340},
  pages     = {1 -- 12},
  year      = {2020},
  abstract  = {Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies.},
  language  = {en}
}