TY - JOUR A1 - Kumar, Reddi K. A1 - Heuchel, Matthias A1 - Kratz, Karl A1 - Lendlein, Andreas A1 - Jankowski, Joachim A1 - Tetali, Sarada D. T1 - Effects of extracts prepared from modified porous poly(ether imide) microparticulate absorbers on cytotoxicity, macrophage differentiation and proinflammatory behavior of human monocytic (THP-1) cells JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Remaining uremic toxins in the blood of chronic renal failure patients represent one central challenge in hemodialysis therapies. Highly porous poly(ether imide) (PEI) microparticles have been recently introduced as candidate absorber materials, which show a high absorption capacity for uremic toxins and allow hydrophilic surface modification suitable for minimization of serum protein absorption. In this work, the effects of extracts prepared from PEI microparticles modified by nucleophilic reaction with low molecular weight polyethylene imine (Pei) or potassium hydroxide (KOH), on human monocytic (THP-1) cells are studied. The obtained results suggested that the extracts of Pei and KOH modified PEI absorbers have no negative effect on THP-1 cell viability and do not initiate the critical differentiation towards macrophages. The extracts did not enhance transcript or protein levels of investigated proinflammatory markers in THP-1 cells, namely, TNF alpha, MCP1, IL6 and IL8. Based on these findings such modified PEI microparticles should be qualified for further pre-clinical evaluation i.e. in an in vivo animal experiment. KW - Chronic kidney disease KW - hemodialysis KW - Inflammation KW - Porous poly(ether imide) microparticulate absorbers KW - THP-1 cells KW - Uremic toxins Y1 - 2018 U6 - https://doi.org/10.3233/CH-189112 SN - 1386-0291 SN - 1875-8622 VL - 69 IS - 1-2 SP - 175 EP - 185 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Sadowska, Aleksandra A1 - Touli, Ermioni A1 - Hitzl, Wolfgang A1 - Greutert, Helen A1 - Ferguson, Stephen J. A1 - Würtz-Kozak, Karin A1 - Hausmann, Oliver N. T1 - Inflammaging in cervical and lumbar degenerated intervertebral discs BT - analysis of proinflammatory cytokine and TRP channel expression JF - European Spine Journal N2 - To investigate and compare the occurrence of inflammatory processes in the sites of disc degeneration in the lumbar and cervical spine by a gene array and subsequent qPCR and to investigate the mechanistic involvement of transient receptor potential channels TRPC6 and TRPV4. The gene expression of inflammatory cytokines and TRP channels was measured in human disc samples obtained from patients undergoing discectomy at the cervical (n = 24) or lumbar (n = 27) spine for degenerative disc disease (DDD) and disc herniation (DH) and analyzed for differences with regard to spinal level, IVD degeneration grade, Modic grade, age, sex, disc region and surgical extent. Aside from genes with known implication in DDD and DH, four previously unreported genes from the interferon and TRP families (IFNA1, IFNA8, IFNB1, TRPC6) could be detected. A correlation between gene expression and age (IL-15) and IVD degeneration grade (IFNA1, IL-6, IL-15, TRPC6), but not Modic grade, was identified. Significant differences were detected between cervical and lumbar discs (IL-15), nucleus and annulus (IL-6, TNF-alpha, TRPC6), single-level and multi-level surgery (IL-6, IL-8) as well as DDD and DH (IL-8), while sex had no effect. Multiple gene-gene pair correlations, either between different cytokines or between cytokines and TRP channels, exist in the disc. This study supports the relevance of IL-6 and IL-8 in disc diseases, but furthermore points toward a possible pathological role of IL-15 and type I interferons, as well as a mechanistic role of TRPC6. With limited differences in the inflammatory profile of cervical and lumbar discs, novel anti-inflammatory or TRP-modulatory strategies for the treatment of disc pathologies may be applicable independent of the spinal region. KW - Cervical and lumbar discs KW - Degenerative disc disease (DDD) and disc herniation (DH) KW - Inflammaging KW - Inflammation KW - Intervertebral disc KW - Transient receptor potential (TRP) channel Y1 - 2017 U6 - https://doi.org/10.1007/s00586-017-5360-8 SN - 0940-6719 SN - 1432-0932 VL - 27 IS - 3 SP - 564 EP - 577 PB - Springer CY - New York ER - TY - JOUR A1 - Dschietzig, Thomas Bernd A1 - Krause-Relle, Katharina A1 - Hennequin, Maud A1 - von Websky, Karoline A1 - Rahnenfuhrer, Jan A1 - Ruppert, Jana A1 - Groena, Hans Juergen A1 - Armbruster, Franz Paul A1 - Bathgate, Ross A. D. A1 - Aschenbach, Joerg R. A1 - Forssmann, Wolf-Georg A1 - Hocher, Berthold T1 - Relaxin-2 does not Ameliorate Nephropathy in an experimental model of Type-1 Diabetes JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie N2 - Background/Aims: In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 mu g/kg/day) and high-dose (320 mu g/kg/day) Rlx were tested against vehicle (n = 20 each) and non-diabetic controls (n = 14) for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO) mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-beta pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-beta-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes. KW - Diabetic nephropathy KW - Diabetic cardiomyopathy KW - Fibrosis KW - Inflammation KW - Relaxin Y1 - 2015 U6 - https://doi.org/10.1159/000368484 SN - 1420-4096 SN - 1423-0143 VL - 40 IS - 1 SP - 77 EP - 88 PB - Karger CY - Basel ER - TY - JOUR A1 - Maschirow, Laura A1 - Khalaf, Kinda A1 - Al-Aubaidy, Hayder A. A1 - Jelinek, Herbert F. T1 - Inflammation, coagulation, endothelial dysfunction and oxidative stress in prediabetes - Biomarkers as a possible tool for early disease detection for rural screening JF - Clinical biochemistry : official journal of the Canadian Society of Clinical Chemists N2 - Objectives: This study aims to increase understanding of the connection between oxidative stress and inflammation in diabetes disease progression to provide a basis for investigating improved diagnostic possibilities, treatment and prevention of prediabetes. Design and methods: Differences in the level of biochemical markers of oxidative stress (erythrocyte GSH/GSSG and urinary 8-isoprostane), inflammation (CRP, IL-6), endothelial dysfunction (plasma homocysteine, urinary 8-hydroxy-2-deoxy-guanosine) and coagulation/fibrinolysis (C5a, D-Dimer) were determined in prediabetes and control subjects. Results: While no difference was found in the 8-isoprostane levels between the two groups, the erythrocyte GSH/GSSG ratio was significantly reduced in the prediabetes group compared to control, indicating increased oxidative stress in the prediabetic state. Both urinary 8-OHdG and surprisingly also plasma homocysteine were significantly elevated in the prediabetes group, indicating endothelial dysfunction. The inflammation markers were slightly elevated in the prediabetic subjects and the same trend was found for the coagulation/fibrinolysis markers C5a and D-Dimer. These results were however not significant. Conclusions: The small elevation of blood glucose levels in the prediabetic state may have a detectable influence on endothelial function as indicated by changes to 8-OHdG, indicating an increased DNA-damage and homocysteine release from endothelial cells. Increased oxidative stress as indicated by the reduced GSH/GSSG ratio is likely to be the link between the moderate hyperglycaemia in prediabetes and pathological changes in endothelial function, which in the long-term may promote atherogenesis and result in the development of cardiovascular disease. Early detection of prediabetes is essential to avoid diabetes development and the associated complications like cardiovascular disease. The GSH/GSSG ratio and biomarkers like urinary 8-OHdG and plasma homocysteine offer a possible tool for the assessment of prediabetes in prevention screenings. (C) 2015 The Authors. The Canadian Society of Clinical Chemists. Published by Elsevier Inc. KW - Prediabetes KW - Oxidative stress KW - Inflammation KW - Coagulation KW - Endothelial dysfunction Y1 - 2015 U6 - https://doi.org/10.1016/j.clinbiochem.2015.02.015 SN - 0009-9120 SN - 1873-2933 VL - 48 IS - 9 SP - 581 EP - 585 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Arlt, Olga A1 - Schwiebs, Anja A1 - Japtok, Lukasz A1 - Rueger, Katja A1 - Katzy, Elisabeth A1 - Kleuser, Burkhard A1 - Radeke, Heinfried H. T1 - Sphingosine-1-Phosphate modulates dendritic cell function: focus on non-migratory effects in vitro and in vivo JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology N2 - Dendritic cells (DCs) are the cutting edge in innate and adaptive immunity. The major functions of these antigen presenting cells are the capture, endosomal processing and presentation of antigens, providing them an exclusive ability to provoke adaptive immune responses and to induce and control tolerance. Immature DCs capture and process antigens, migrate towards secondary lymphoid organs where they present antigens to naive T cells in a well synchronized sequence of procedures referred to as maturation. Indeed, recent research indicated that sphingolipids are modulators of essential steps in DC homeostasis. It has been recognized that sphingolipids not only modulate the development of DC subtypes from precursor cells but also influence functional activities of DCs such as antigen capture, and cytokine profiling. Thus, it is not astonishing that sphingolipids and sphingolipid metabolism play a substantial role in inflammatory diseases that are modulated by DCs. Here we highlight the function of sphingosine 1-phosphate (S1P) on DC homeostasis and the role of SIP and SW metabolism in inflammatory diseases. KW - Sphingosine-1-phosphate KW - Dendritic cells KW - Fingolimod KW - IL-12 KW - Inflammation Y1 - 2014 U6 - https://doi.org/10.1159/000362982 SN - 1015-8987 SN - 1421-9778 VL - 34 IS - 1 SP - 27 EP - 44 PB - Karger CY - Basel ER - TY - JOUR A1 - Pieper, Christian A1 - Marek, Jasmin Jacqueline A1 - Unterberg, Marlies A1 - Schwerdtle, Tanja A1 - Galla, Hans-Joachim T1 - Brain capillary pericytes contribute to the immune defense in response to cytokines or LPS in vitro JF - Brain research : an international multidisciplinary journal devoted to fundamental research in the brain sciences N2 - The prevention of an inflammation in the brain is one of the most important goals the body has to achieve. As pericytes are located on the abluminal side of the capillaries in the brain, their role in fighting against invading pathogens has been investigated in some points, mostly in their ability to behave like macrophages. Here we studied the potential of pericytes to react as immune cells under inflammatory conditions, especially regarding the expression of the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), major histocompatibility complex II (MHC II) molecules, CD68, as well as the generation of reactive oxygen and nitrogen species (RONS), and their ability in phagocytosis. Quantitative real time PCR and western blot analysis showed that pericytes are able to increase the expression of typical inflammatory marker proteins after the stimulation with tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), interferon-gamma (IFN-gamma), or lipopolysaccharides (LPS). Depending on the different specific pro-inflammatory factors pericytes changed the expression of alpha smooth muscle actin (alpha SMA), the most predominant pericyte marker. We conclude that the role of the pericytes within the immune system is regulated and fine-tuned by different cytokines strongly depending on the time when the cytokines are released and their concentration. The present results will help to understand the pericyte mediated defense mechanisms in the brain. KW - Pericytes KW - Cytokines KW - Inflammation KW - LPS KW - Macrophage-like phenotype Y1 - 2014 U6 - https://doi.org/10.1016/j.brainres.2014.01.004 SN - 0006-8993 SN - 1872-6240 VL - 1550 SP - 1 EP - 8 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Schaefer, H. A1 - Kohn, B. A1 - Schweigert, Florian J. A1 - Raila, Jens T1 - Quantitative and Qualitative Urine Protein Excretion in Dogs with Severe Inflammatory Response Syndrome JF - JOURNAL OF VETERINARY INTERNAL MEDICINE N2 - Background: Proteinuria is an established characteristic of renal disease in dogs, providing diagnostic and prognostic information. Little is known about the occurrence and severity of proteinuria in dogs with severe inflammatory response syndrome (SIRS). Hypothesis: The quantitative and qualitative urinary protein (UP) excretion is altered in dogs with SIRS. Animals: Thirty-nine dogs with SIRS and 15 healthy control dogs at admission. Methods: A case control study was performed. Diagnosis of SIRS was based on clinical and clinicopathological findings. Urinary protein (UP) was measured by a colorimetric assay. Urinary albumin (UAlb) and urinary retinol-binding protein (URBP) were measured by ELISA and quantified in relation to urinary creatinine (UC). Sodium dodecyl sulfate polyacrylamid-gel electrophoresis was conducted to identify the qualitative pattern of proteinuria. Mann-Whitney U-test was used to assess differences in UP/UC, UAlb/UC and URBP/UC between the groups. P-values <.05 were considered significant. Results: Dogs with SIRS had higher ratios of UP/UC, UAlb/UC and URBP/UC (all P <.001) in comparison to healthy control dogs. Dogs with SIRS had a total of 11 protein bands compared to 3 bands in healthy controls. In dogs with SIRS, 58% of the total counted bands were in the low molecular weight range (< 60 kDa) whereas 42% were in the middle (60-80 kDa)/high molecular weight range (>80 kDa). Conclusions and Clinical Importance: SIRS alters UP excretion in dogs. Further studies should evaluate whether or not the magnitude of proteinuria is predictive of the severity and outcome of dogs with SIRS. KW - Albumin KW - Inflammation KW - Proteinuria KW - Retinol-binding protein Y1 - 2011 U6 - https://doi.org/10.1111/j.1939-1676.2011.00829.x SN - 0891-6640 VL - 25 IS - 6 SP - 1292 EP - 1297 PB - WILEY-BLACKWELL CY - MALDEN ER -