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  - THES
A1  - Kamann, Stefanie
T1  - Die Bedeutung von Entzündung und reaktiven Sauerstoffspezies in der Intimahyperplasie
T1  - The role of inflammation and reactive oxygen species in intimal hyperplasia
N2  - Die Restenose stellt ein zentrales Problem der interventionellen Kardiologie dar und ist häufigste Komplikation nach perkutanen Angioplastieverfahren. Hauptursache dieser Wiederverengung des Gefäßes ist die Bildung einer Neointima durch die Proliferation transdifferenzierter vaskulärer glatter Muskelzellen und die Sekretion extrazellulärer Matrix. Die Entstehung reaktiver Sauerstoffspezies (ROS) und die Entzündungsreaktion nach der Gefäßverletzung werden als frühe, die Neointimabildung induzierende Prozesse diskutiert. Im Rahmen dieser Arbeit wurden mehrere Projekte bearbeitet, die Aufschluss über die während der Neointimabildung statt findenden Prozesse geben sollen. Mit Hilfe eines Verletzungsmodells der murinen Femoralarterie wurde der Einfluss der Entzündung und der ROS-Bildung auf die Neointimabildung in der Maus untersucht. Die Behandlung mit dem mitochondrialen Superoxiddismutase-Mimetikum MitoTEMPO verminderte die Bildung der Neointima besser, als die Behandlung mit dem globalen ROS-Fänger N-Acetylcystein. Die stärkste Hemmung der Neointimabildung wurde jedoch durch die Immunsuppression mit Rapamycin erreicht. Interferon-γ (INFγ) ist ein wichtiges Zytokin der Th1-Immunantwort, das in Folge der Gefäßverletzung freigesetzt wird und die proinflammatorischen Chemokine CXCL9 (MIG, Monokine Induced by INF), CXCL10 (IP-10, INF inducible Protein of 10 kDa) und CXCL11 (I-TAC, Interferon inducible T cell-Chemoattractant) induziert. CXCL9, CXCL10 und CXCL11 sind Liganden des CXC-Chemokinrezeptors 3 (CXCR3) und locken chemotaktisch CXCR3 positive Entzündungszellen zum Ort der Gefäßverletzung. Daher wurde die spezielle Bedeutung des Chemokins CXCL10 in der Restenose untersucht. Dazu wurden CXCL10-defiziente Mäuse dem Femoralisverletzungsmodell unterzogen und die Gefäße nach 14 Tagen morphometrisch und immunhistologisch untersucht. CXCL10-Defizienz führte in Mäusen zu einer verminderten Neointimabildung, die mit einer verringerten Inflammation, Apoptose und Proliferation im verletzten Gefäß korrelierte. Neben der Inflammation beeinflusst aber auch die Reendothelialisierung der verletzten Gefäßwand die Restenose. Interessanterweise war im Vergleich zu Wildtyp-Mäusen in den CXCL10-Knockout-Mäusen auch die Reendothelialisierung erheblich verbessert. Offensichtlich ist das CXCR3-Chemokinsystem also in völlig unterschiedliche biologische Prozesse involviert und beeinflusst nicht nur die Bildung der Neoimtima durch die Förderung der Entzündung, sondern auch die Unterdrückung der Reendothelialisierung der verletzten Gefäßwand. Tatsächlich wird der CXCR3 nicht nur auf Entzündungszellen, sondern auch auf Endothelzellen exprimiert. Zur separaten Untersuchung der Rolle des CXCR3 in der Inflammation und der Reendothelialisierung wurde im Rahmen dieser Arbeit damit begonnen konditionelle CXCR3-Knockout-Mäuse zu generieren, in denen der CXCR3 entweder in Entzündungszellen oder in Endothelzellen ausgeschaltet ist. Zum besseren Verständnis der molekularen Mechanismen, mit denen der CXCR3 seine Funktionen vermittelt, wurde zudem untersucht ob dieser mit anderen G-Protein-gekoppelten Rezeptoren (GPCR) interagiert. Die Analyse von Coimmunpräzipitaten deutet auf eine Homodimerisierung der beiden CXCR3 Splicevarianten CXCR3A und CXCR3B, sowie auf die Heterodimerbildung von CXCR3A und CXCR3B mit sich, sowie jeweils mit CCR2, CCR3, CCR5 und den Opioidrezeptoren MOR und KOR hin. Die getestete Methode des Fluoreszenz-Resonanz-Energietransfers (FRET) erwies sich jedoch als ungeeignet zur Untersuchung von CXCR3, da dieser in HEK293T-Zellen nicht korrekt transient exprimiert wurde. Insgesamt deuten die Ergebnisse dieser Arbeit darauf hin, dass das CXCR3-Chemokinsystem eine zentrale Rolle in unterschiedlichen, die Neointimabildung beeinflussenden Prozessen spielt. Damit könnten der CXCR3 und insbesondere das Chemokin CXCL10 interessante Zielmoleküle in der Entwicklung neuer verbesserter Therapien zur Verhinderung der Restenose darstellen.
N2  - Restenosis represents a central problem after coronary angioplasty procedures and is caused by intimal hyperplasia, also called neointima, as a result of transdifferentiation, proliferation of vascular smooth muscle cells and secretion of extracellular matrix. Formation of reactive oxygen species (ROS) and inflammation after vascular injury caused by angioplasty are discussed as early inducers of neointima formation. In several projects the processes causing the development of intimal hyperplasia were investigated. First of all, the impact of inflammation and ROS in neointima formation was investigated using the mouse femoral injury model. The mitochondrial superoxide dismutase mimetic mitoTEMPO could reduce neointima formation better than the global ROS scavenger N-acetylcystein. However, the strongest reduction of neointima formation was achieved by the treatment with the immunosuppressant rapamycin. Interferon-γ(INFγ) is a major cytokine of the Th1 immune response. It is released as a result of vessel injury and induces the proinflammatory chemokines CXCL9 (MIG, Monokine Induced by INF), CXCL10 (IP-10, INF inducible Protein of 10 kDa) and CXCL11 (I-TAC, Interferon inducible T-cell-Chemoattractant), which are ligands of the CXC chemokine receptor 3 (CXCR3) and by this chemotactically recruit CXCR3 positive cells to the site of vessel injury. In this work the special role of CXCL10 in restenosis was investigated. Therefore, CXCL10 decient mice underwent the mouse femoral injury model. The vessels were analysed morphometrically and immunohistologically 14 days after injury. CXCL10 deciency lead to decreased neointima formation that correlated with a reduced recruitment of inflammatory cells as well as diminished numbers of apoptotic and proliferating cells at the site of vessel injury. In addition to inflammation the reconstitution of the endothelium has also impact on the development of restenosis. Interestingly reendothelialisation was strongly improved in CXCL10 decient mice compared to wildtype mice. Obviously the CXCR3 chemokine system is involved in different biological prosesses and impairs neointima formation on one hand by the advancement of inflammation and on the other hand by the suppression of reendothelialisation. In fact the CXCR3 is not only expressed on inflammatory cells but also on endothelial cells. To investigate the role of CXCR3 in inflammation and reendothelialisation separatly the generation of conditional CXCR3 knockout mice with a CXCR3 knockout in T-cells or endothelial cells was started in an additional project. For a better understanding of the molecular mechanisms on which the CXCR3 mediates its biological functions the protein-protein interactions of the CXCR3 with other G-protein coupled recteptors (GPCR) was analysed. Coimmunoprecipitation showed homodimerization of the CXCR3 splice variants CXCR3A and CXCR3B, as well as heterodimerization of CXCR3A and CXCR3B with each other and with the chemokine receptors CXCR4, CCR2, CCR3, CCR5 and the opioid receptors MOR and KOR. The additional tested Fluorecence resonance energy transfer (FRET) method proved to be not suitable to measure interactions of CXCR3, since this receptor could not be expressed correctly on the cell surface after transient transfection. To summarise, the results indicate that the CXCR3 chemokine system plays a central role in different processes that mediate neointima formation. Thus, the CXCR3 and especially the chemokine CXCL10 could be interesting therapeutic targets in the development of new or improved treatments to reduce the risk of restenosis.
KW  - Intimahyperplasie
KW  - Neointima
KW  - Reaktive Sauerstoffspezies
KW  - Entzündung
KW  - CXCL10
KW  - Intimal Hyperplasia
KW  - Neointima
KW  - Reactive Oxygen Species
KW  - Inflammation
KW  - CXCL10
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-64683
ER  - 
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  - GEN
A1  - Scholtka, Bettina
A1  - Kühnel, Dana
A1  - Taugner, Felicitas
A1  - Steinberg, Pablo
T1  - Inflammation does not precede or accompany the induction of perneoplastic lesions in the colon of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-fed rats
N2  - Heterocyclic aromatic amines (HCAs) are formed in meat cooked at high temperatures for a long time or over an open flame. In this context 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant HCA in cooked meat, has been suggested to be involved in colon and prostate carcinogenesis. In the latter case it has been reported that: (1) roughly 50% of Fischer F344 male rats treated with PhIP develop carcinomas in the ventral prostate lobe at 1 year of age; (2) inflammation precedes prostatic intraepithelial neoplasia in PhIP-fed rats; (3) inflammation specifically occurs in the ventral prostate lobe of PhIP-fed rats. To test whether PhIP by itself leads to inflammation in the colon and whether a human-relevant concentration of PhIP is able to induce preneoplastic lesions in the colon, male F344 rats were fed 0.1 or 100 ppm PhIP for up to 10 months and thereafter the colon tissue was analyzed histochemically. In none of the experimental groups signs of acute or chronic colonic inflammation were observed. 0.1 ppm PhIP leads to the development of hyperplastic and dysplastic lesions in the colon of single animals, but the incidence of these lesions does not reach a statistical significance. In contrast, in rats fed 100 ppm PhIP for 10 months hyperplastic and dysplastic colonic lesions were induced in a statistically significant number of animals. It is concluded that: (1) the induction of preneoplastic lesions in rat colon by PhIP is not preceded or accompanied by an inflammatory process; (2) a human-relevant concentration of PhIP alone is not sufficient to initiate colon carcinogenesis in rats.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 119 
KW  - Colorectal cancer
KW  - Heterocyclic aromatic amines
KW  - Inflammation
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-44570
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  - 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  - 
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  - 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  -