TY  - JOUR
AB  - BACKGROUND: Serine protease-like (Spl) proteins produced by Staphylococcus (S.) aureus have been associated with allergic inflammation. However, effects of Spls on the epidermal immune response have not been investigated. OBJECTIVES: To assess the epidermal immune response to SplA, SplD and SplE dependent on differentiation of keratinocytes and a Th2 or Th17 cytokine milieu. METHODS: Human keratinocytes of healthy controls and a STAT3-hyper-IgE syndrome (STAT3-HIES) patient were cultured in different calcium concentrations in the presence of Spls and Th2 or Th17 cytokines. Keratinocyte-specific IL-8 production and concomitant migration of neutrophils were assessed. RESULTS: SplE and more significantly SplA, induced IL-8 in keratinocytes. Suprabasal-like keratinocytes showed a higher Spl-mediated IL-8 production and neutrophil migration compared to basal-like keratinocytes. Th17 cytokines amplified Spl-mediated IL-8 production, which correlated with neutrophil recruitment. Neutrophil recruitment by keratinocytes of the STAT3-HIES patient was similar to healthy control cells. CONCLUSION: S. aureus-specific Spl proteases synergized with IL-17A on human keratinocytes with respect to IL-8 release and neutrophil migration, highlighting the importance of keratinocytes and Th17 immunity in barrier function.
AU  - De Donato, D.P.*
AU  - Effner, R.
AU  - Nordengrün, M.*
AU  - Lechner, A.*
AU  - Darisipudi, M.N.*
AU  - Volz, T.*
AU  - Hagl, B.
AU  - Bröker, B.M.*
AU  - Renner, E.D.
C1  - 70782
C2  - 55890
CY  - 24-28 Oval Rd, London Nw1 7dx, England
TI  - Staphylococcus aureus Serine protease-like protein A (SplA) induces IL-8 by keratinocytes and synergizes with IL-17A.
JO  - Cytokine
VL  - 180
PB  - Academic Press Ltd- Elsevier Science Ltd
PY  - 2024
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - BACKGROUND: Obesity is known to be a pro-inflammatory condition affecting multiple organs. Obesity as a systemic pro-inflammatory state, might be associated with bronchial inflammation in non-smoking adolescents with a BMI ≥ 30 kg/m2 without evidence of concomitant chronic diseases. MATERIALS AND METHODS: We studied non-asthmatic obese patients (n = 20; median age 15.8 years; BMI 35.0 kg/m2) compared to age matched healthy control subjects (n = 20; median age 17.5 years; BMI 21.5 kg/m2). Induced sputum differential cell counts and sputum mRNA levels were assessed for all study subjects. Serum levels of CRP, IL-6, and IL-8 were measured. Further, IL-5, IL-6, IL-8, IL-13, IL-17, TNF-α, IFN-γ, and IP-10 protein levels were analyzed in induced sputum was. RESULTS: Serum CRP levels, sputum inflammatory cell load and sputum eosinophils differed significantly between obese and non-obese subjects, for sputum neutrophils, a correlation was shown with BMI ≥ 30 kg/m2. Differences were also observed for sputum mRNA expression of IL6, IL8, IL13, IL17, IL23, and IFN-γ, as well as the transcription factors T-bet, GATA3, and FoxP3. CONCLUSIONS: Increased bronchial inflammation, triggered by systemic or local inflammatory effects of obesity itself, may account for the higher rates of airway disease in obese adolescents.
AU  - Gutmann, D.*
AU  - Dressler, M.*
AU  - Eickmeier, O.*
AU  - Herrmann, E.*
AU  - Kirwil, M.*
AU  - Schubert, R.*
AU  - Zielen, S.*
AU  - Zissler, U.M.
C1  - 68880
C2  - 53735
CY  - 24-28 Oval Rd, London Nw1 7dx, England
TI  - Proinflammatory pattern in the lower airways of non-asthmatic obese adolescents.
JO  - Cytokine
VL  - 173
PB  - Academic Press Ltd- Elsevier Science Ltd
PY  - 2023
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - Background: The renal tubular glycoprotein uromodulin is associated with obesity and type 2 diabetes, but the underlying mechanisms are elusive. We investigated the association of serum uromodulin with adipokines and tested the effect modification by diabetes status. Methods: The associations of serum uromodulin with eight adipokines were assessed in 795–1080 participants of the KORA F4 study aged 62–81 years using linear regression models adjusted for sex, age, BMI, estimated glomerular filtration rate and diabetes. Significant associations were assessed for effect modification by diabetes status. We further tested using logistic regression whether adjustment for the significant adipokines affected the association of uromodulin with type 2 diabetes. Results: Serum uromodulin was inversely associated with chemerin and retinol-binding protein-4 after multivariable adjustment (p < 0.001) and Bonferroni correction for multiple testing. No significant association was observed between uromodulin and the other adipokines (leptin, adiponectin, secreted frizzled-related protein 5, progranulin, omentin-1 and vaspin) after correcting for multiple testing. The association of uromodulin with chemerin and retinol-binding protein-4 was stronger in participants with type 2 diabetes than in participants without diabetes (p for interaction < 0.05). However, inclusion of chemerin and retinol-binding protein-4 in logistic regression models did not attenuate the association of serum uromodulin with diabetes. Conclusions: Serum uromodulin was inversely associated with the predominantly pro-inflammatory adipokines chemerin and retinol-binding protein-4. The associations were stronger in participants with type 2 diabetes compared to participants without diabetes. However, the association of serum uromodulin with type 2 diabetes was independent of chemerin and retinol-binding protein-4.
AU  - Then, C.
AU  - Herder, C.*
AU  - Thorand, B.
AU  - Sujana, C.
AU  - Heier, M.
AU  - Meisinger, C.
AU  - Peters, A.
AU  - Koenig, W.*
AU  - Rathmann, W.*
AU  - Roden, M.*
AU  - Stumvoll, M.*
AU  - Maalmi, H.*
AU  - Then, H.*
AU  - Ferrari, U.*
AU  - Scherberich, J.*
AU  - Seissler, J.
C1  - 63831
C2  - 51766
TI  - Association of serum uromodulin with adipokines in dependence of type 2 diabetes.
JO  - Cytokine
VL  - 150
PY  - 2022
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - Aims: Adipose tissue-secreted proteins, i.e. adipocytokines, have been identified as potential mediators linking fat mass and adipose tissue dysfunction with impaired glucose homeostasis, alterations in the inflammatory status, and risk of diabetes. The aim of this study was to determine whether seven circulating adipocytokines are associated with gestational diabetes mellitus (GDM) or are altered by metabolic and weight changes during pregnancy itself.Methods: A panel of seven adipocytokines (i.e. adiponectin, adipocyte fatty acid-binding protein, chemerin, leptin, Pro-Enkephalin, progranulin, and Pro-Neurotensin) was quantified in serum in a cross-sectional cohort of 222 women with the following three groups matched for age and body mass index: (i) 74 pregnant women with GDM; (ii) 74 pregnant women without GDM; and (iii) 74 non-pregnant and healthy women. A stepwise statistical approach was used by performing pairwise comparisons, principal component analysis (PCA), and partial least square discriminant analysis (PLS-DA).Results: Five out of seven adipocytokines were dysregulated between pregnant and non-pregnant women, i.e. adiponectin, chemerin, leptin, Pro-Enkephalin, and progranulin. None of the adipocytokines significantly differed between GDM and non-GDM status during pregnancy. The same five adipocytokines clustered in a principal component representing pregnancy-induced effects. Fasting insulin was the most relevant parameter in the discrimination of GDM as compared to pregnant women without GDM, whereas chemerin and adiponectin were most relevant factors to discriminate pregnancy status.Conclusions: Pregnancy status but not presence of GDM can be distinguished by the seven investigated adipocytokines in discrimination analyses.
AU  - Ebert, T.*
AU  - Gebhardt, C.*
AU  - Scholz, M.*
AU  - Schleinitz, D.*
AU  - Blüher, M.
AU  - Stumvoll, M.*
AU  - Kovacs, P.*
AU  - Fasshauer, M.*
AU  - Tönjes, A.*
C1  - 58841
C2  - 48629
CY  - 24-28 Oval Rd, London Nw1 7dx, England
TI  - Adipocytokines are not associated with gestational diabetes mellitus but with pregnancy status.
JO  - Cytokine
VL  - 131
PB  - Academic Press Ltd- Elsevier Science Ltd
PY  - 2020
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - Background and objective: Anti-angiogenic treatment has been recently shown to be clinically beneficial for mesothelioma patients. Angiopoietins-1 and -2 are key regulators of tumor angiogenesis. Ang-1 is mainly known to promote angiogenesis and vessel stability, while Ang-2 could serve as an antagonist of Ang-1 causing vessel regression and destabilization or enhance angiogenesis in a context-dependent manner. We hypothesized that Ang-1 would promote and Ang2 would halt experimental mesothelioma by affecting tumor angiogenesis. Methods: To examine the effects of angiopoietins in mesothelioma angiogenesis and in vivo growth we constructed Ang-1 or Ang-2 overexpressing AE17 and AB1 mesothelioma cells and implanted them in the respective syngeneic animals. We also explored the clinical relevance of our observations using the human tumoral mRNAseq data available in the TCGA database. Results and conclusions: Ang-1 promotes mesothelioma angiogenesis and growth while the effect of Ang-2 is context-dependent. Low Ang-1 levels in human mesotheliomas are associated with the epitheloid subtype. Tumors of high Ang-1, or concurrent high Ang-2 and VEGF expression present high PECAM-1 and CDH5 expression, markers of vascularity and vascular stability, respectively. Our results highlight the importance of angiopoietins in mesothelioma pathophysiology and pave the way for the clinical development of novel anti-angiogenic strategies.
AU  - Magkouta, S.*
AU  - Kollintza, A.*
AU  - Moschos, C.*
AU  - Spella, M.*
AU  - Skianis, I.*
AU  - Pappas, A.*
AU  - Vazakidou, M.E.*
AU  - Stathopoulos, G.T.
AU  - Kalomenidis, I.*
C1  - 54263
C2  - 45461
TI  - Role of angiopoietins in mesothelioma progression.
JO  - Cytokine
PY  - 2018
SN  - 1043-4666
ER  - 

TY  - JOUR
AU  - Borst, K.*
AU  - Frenz, T.*
AU  - Spanier, J.*
AU  - Tegtmeyer, P.*
AU  - Chhatbar, C.*
AU  - Namineni, S.
AU  - Lienenklaus, S.*
AU  - Köster, M.*
AU  - Heikenwälder, M.
AU  - Sutter, G.*
AU  - Kalinke, U.*
C1  - 47116
C2  - 39211
SP  - 108
TI  - In virus-induced hepatitis local IFN-I responses modulate myeloid suppressor cell infiltration.
JO  - Cytokine
VL  - 76
IS  - 1
PY  - 2015
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - BACKGROUND: Airway inflammation plays a major role in the progression of chronic lung diseases. The features of airway inflammation are not well defined among patients with cases of bronchiolitis obliterans (BO) that began in childhood. OBJECTIVES: To investigate the sputum cell and cytokine profiles of stable cases of BO regarding lung function and the involvement of small airway disease (SAD). METHODS: Twenty patients with BO (median age=14.5, range=7-23years) and 22 healthy controls (median age=16.5years, range=7-24years) were investigated. Lung function parameters and bronchial reversibility testing as well as sputum cell and cytokine profiles (IL-1β, IL-6, IL-8, TNF-α, IL-5, IFN-γ, and NFκB regulation) were analysed using quantitative RT-PCR and cytometric bead assay (CBA) in induced sputum. RESULTS: Patients with BO had significantly lower lung function values, including FVC, forced expiratory volume (FEV1), the Tiffeneau index (FEV1/VC), and MEF25, but increased functional residual capacity (RV/TLC) values. Bronchial reversibility was found in five patients (25%). Moreover, airway inflammation (as indicated by total cells, neutrophils, IL-1β, IL-6, IL-8, TNF-α, and NFκB) was significantly increased among patients with BO compared with controls. CONCLUSIONS: BO is predominantly a neutrophilic disease of the small bronchioles featuring elevated levels of pro-inflammatory cytokines leading to tissue remodelling and fibrosis of the small airways. Future therapies for patients with BO should more efficiently target the small airways.
AU  - Rosewich, M.*
AU  - Zissler, U.M.
AU  - Kheiri, T.*
AU  - Voss, S.*
AU  - Eickmeier, O.*
AU  - Schulze, J.*
AU  - Herrmann, E.*
AU  - Dücker, R.P.*
AU  - Schubert, R.*
AU  - Zielen, S.*
C1  - 43716
C2  - 36797
CY  - London
SP  - 156-162
TI  - Airway inflammation in children and adolescents with bronchiolitis obliterans.
JO  - Cytokine
VL  - 73
IS  - 1
PB  - Academic Press Ltd- Elsevier Science Ltd
PY  - 2015
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - Several studies have shown associations of posttraumatic stress disorder (PTSD) with the development of cardiometabolic diseases. The underlying psychopathological mechanisms, including potential links to inflammatory processes, have been discussed but remain elusive. Therefore, the aim of the present study was to evaluate the association of PTSD symptoms with the inflammatory biomarkers C-reactive protein (CRP) and interleukin-18 (IL-18). The study population consisted of 3012 participants aged 32-81years drawn from the population-based KORA F4 study conducted in 2006-08 in the Augsburg region (Southern Germany). PTSD symptoms were measured by the Impact of Event Scale, the Posttraumatic Diagnostic Scale and interview data and classified as no, partial or full PTSD. The associations of PTSD with CRP and IL-18 concentrations were estimated by multiple regression analyses with adjustments for age, sex and cardiometabolic risk factors. Linear regression analyses showed no significant association between PTSD and CRP or IL-18 concentration: adjusted for age and sex, the geometric mean concentrations in participants with full PTSD was for CRP 9% lower and for IL-18 1% higher than in participants with no PTSD (p values 0.53 and 0.89). However, further analyses indicated that individuals with partial PTSD had an increased chance of belonging to the highest quartile of the IL-18 concentration. No significant association was observed for any of the three subscales intrusion, avoidance or hyperarousal with CRP or IL-18 concentration. This large, population-based study could not find an association of full PTSD with CRP and IL-18 concentrations. Further research is needed to analyse these relationships.
AU  - Baumert, J.J.
AU  - Lukaschek, K.
AU  - Kruse, J.*
AU  - Emeny, R.T.
AU  - Koenig, W.*
AU  - von Känel, R.*
AU  - Ladwig, K.-H.
C1  - 24949
C2  - 31730
SP  - 201-208
TI  - No evidence for an association of posttraumatic stress disorder with circulating levels of CRP and IL-18 in a population-based study.
JO  - Cytokine
VL  - 63
IS  - 2
PB  - Academic Press-Elsevier
PY  - 2013
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - nflammatory cytokine TNFα enhances permeability of brain capillaries constituting blood brain barrier (BBB). In the monoculture endothelial models of BBB TNFα alters tight junction (TJ) structure and protein content. Claudin-5 (Cldn5) is a key TJ protein whose expression in the brain endothelial cells is critical to the function of BBB. TNFα reduces Cldn5 promoter activity and mRNA expression in mouse brain derived endothelial cells but the regulatory elements and signaling mechanism involved are not defined. Here we report that TNFα acts through NFκB signaling and requires a conserved promoter region for the down-regulation of Cldn5 expression. Overexpression of the NFκB subunit p65 (RelA) alone repressed Cldn5 promoter activity in mouse brain endothelial cells. We observed partial loss of Cldn5 protein expression after prolonged TNFα treatment in primary endothelial culture isolated from C56BL/6 mice brain. Taken together, our results confirm and extend previous observations of TNFα induced down-regulation of Cldn5 expression in mouse brain endothelial cells.
AU  - Aslam, M.*
AU  - Ahmad, N.
AU  - Srivastava, R.*
AU  - Hemmer, B.*
C1  - 7231
C2  - 29569
SP  - 269-275
TI  - TNF-alpha induced NFκB signaling and p65 (RelA) overexpression repress Cldn5 promoter in mouse brain endothelial cells.
JO  - Cytokine
VL  - 57
IS  - 2
PB  - Elsevier
PY  - 2012
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - Human pancreatic cancer is one of the most fatal of all solid tissue malignancies. Pancreatic inflammation plays a key role in the development of pancreatic malignancy mediated by pro-inflammatory signalling cascades. Despite advances in surgery and radiation oncology, no significant improvements in overall survival have yet been achieved. Recent investigations suggest a crucial role of interleukin-33 (IL-33), a novel IL-1 family cytokine, in the pathogenesis of chronic pancreatitis and possibly pancreatic cancer. However, the precise role of IL-33 in pancreatic carcinogenesis is poorly understood. As IL-33 mediates its effects via the heterodimeric ST2L/IL-1 receptor accessory protein (IL-1RAcP) receptor complex, we investigated the influence of IL-33 alone, IL-33 combined with IL-1 and other inflammatory cytokines on IL-33 receptor/ligand mRNA expression and production of tumorigenic factors in the highly metastatic human pancreatic adenocarcinoma cell line Colo357. Our results demonstrated that IL-1 and IL-3 up-regulated IL-33 mRNA while IL-12 showed the opposite effect. We also detected a counter-regulatory effect of IL-33 and IL-1 on the mRNA expression of soluble IL-33 receptor ST2 and membrane-bound receptor ST2L. Furthermore, IL-33 and IL-1 acted synergistically in up-regulating secretion of pro-inflammatory IL-6. IL-33 alone stimulated spontaneous release of pro-angiogenic IL-8, but it did not affect IL-1-induced IL-8 secretion. IL-33/IL-1 effects on cytokine production appear to be mediated via NF-κB activation. These data argue for the pro-inflammatory role of IL-33 in Colo357 cells implying that IL-33 might act as a crucial mediator in inflammation-associated pancreatic carcinogenesis.
AU  - Schmieder, A.*
AU  - Multhoff, G.
AU  - Radons, J.*
C1  - 8317
C2  - 29382
SP  - 514-521
TI  - Interleukin-33 acts as a pro-inflammatory cytokine and modulates its receptor gene expression in highly metastatic human pancreatic carcinoma cells.
JO  - Cytokine
VL  - 60
IS  - 2
PB  - Elsevier
PY  - 2012
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, P<0.05) and IL-6 (2.7+/-0.1pg/mL vs. CTRL 2.1+/-0.1, P<0.05) were both elevated in subjects with MI. These increases were particularly pronounced in the presence of concomitant CHF (both P<0.01 vs. CTRL) and LV dysfunction (EF<45%, both P<0.05 vs. CTRL). However, NT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all P<0.05) upon regression analysis whereas IL-6 was only correlated with history of MI (P<0.001). Accordingly, MI subjects with symptomatic LV dysfunction were detected by NT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both P<0.05) but with a much greater absolute activation of BNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; P<0.001) than IL-6 (r=-0.53; P=0.001) and was a markedly more sensitive and specific molecular marker of LV dysfunction (sensitivity 91%, specificity 100%, ROC-area 0.94) than IL-6 (sensitivity 74%, specificity 83%, ROC-area 0.87). Our animal study provides evidence that IL-6 expression is activated in heart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure.
AU  - Birner, C.M.*
AU  - Ulucan, C.*
AU  - Fredersdorf, S.*
AU  - Rihm, M.
AU  - Löwel, H.
AU  - Stritzke, J.*
AU  - Schunkert, H.*
AU  - Hengstenberg, C.*
AU  - Holmer, S.*
AU  - Riegger, G.*
AU  - Luchner, A.*
C1  - 4026
C2  - 25018
SP  - 89-97
TI  - Head-to-head comparison of BNP and IL-6 as markers of clinical and experimental heart failure: Superiority of BNP.
JO  - Cytokine
VL  - 40
IS  - 2
PB  - Saunders
PY  - 2007
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - The erythroid differentiation regulator (EDR) is a highly conserved autocrine factor produced in many tissues. Its haemoglobin synthesis-inducing activity for human and murine erythroleukaemia cell lines had been detected in WEHI-3 conditioned medium. EDR functions were analysed in detail. It is released from cells immediately in response to various stressful conditions and enhances cell survival particularly at a lower concentration range and low cell density. At high cell density and high EDR concentration the opposite effect of an increase in cell death was observed. Its essential function within a tissue is considered to be the maintenance of growth homeostasis.
      
      	Cells kept in culture for weeks show a decreasing responsiveness to EDR supply. This was also noted in freshly cloned EDR-responsive mouse erythroleukaemia cells pointing to a molecular adaptation process. Human haematopoietic progenitors were amplified 7-fold by EDR when kept at low cytokine levels. At saturating levels progenitors giving rise to at least two lineages in semisolid medium (E-mix) respond to EDR with an average 1.87-fold increase in colony numbers and a bell-shaped dose–response curve. Of the more mature BFU-E compartment a response was observed particularly in cases with low colony numbers. Given the release from irradiated stromal cells and the ability to partly substitute for stromal cells in the Burkitt's lymphoma cell line BL-70, EDR functions as a stromal survival factor for stroma-responsive cells.
AU  - Dörmer, P.*
AU  - Spitzer, E.
AU  - Möller, W.
C1  - 3184
C2  - 21971
SP  - 47-57
TI  - EDR is a stress-related survival factor from stroma and other tissues acting on early haematopoitic progenitors (E-Mix).
JO  - Cytokine
VL  - 27
IS  - 2-3
PY  - 2004
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - In serum-free WEHI-3 supernatants an activity was detected inducing haemoglobin synthesis in human and murine erythroleukaemia cell lines. The absolute numbers of benzidine-positive cells induced with either DMSO or WEHI-3-conditioned medium were comparable. Terminal differentiation was not observed. An expression library from WEHI-3 RNA aided by PCR cloning revealed an open reading frame corresponding to a 209 amino acid protein. This was 100% identical to a sequence from human stimulated peripheral blood mononuclear cells. In contrast to human RNA, mouse RNA exhibited multiple bands of pre-mRNA in Northern blots. The gene was provisionally termed erythroid differentiation regulator (edr).
      
      	In mammalian cells EDR is mostly expressed as a 56 kDa dimer showing higher activity than the recombinant monomer. The activity profile is bell-shaped. Expression was observed in many normal mouse tissues, yet in haematopoiesis it was largely confined to CD34+ cells. It was enhanced by a series of stimuli such as phorbol ester, and transformed cells generally showed a higher level of EDR expression than normal ones. The protein is localized at the inner side of the cytoplasmic membrane and is released in part via vesicles. In view of the broad range of EDR-expressing tissues the function obviously exceeds haemoglobin synthesis induction. Involvement in cell survival and growth control has been observed and will be dealt with in detail elsewhere.
AU  - Dörmer, P.
AU  - Spitzer, E.
AU  - Frankenberger, M.
AU  - Kremmer, E.
C1  - 4134
C2  - 21896
SP  - 231-242
TI  - Erythroid differentiation regulator (EDR), a novel, highly conserved factor I. induction of haemoglobin synthesis in erythroleukaemic cells.
JO  - Cytokine
VL  - 26
IS  - 6
PY  - 2004
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - The CD34-negative, adherent growing, fibroblast-like canine haematopoietic stem cell line D064 was recently identified as the earliest progenitor population in the bone marrow. D064 cells are predominately quiescent. Quiescence is mediated by the accumulation of the cyclin-dependent kinase inhibitor p27kip-1and in parallel, by the downregulation of Cyclin B, leading to an accumulation of quiescent cells in the G0/G1-phase of the cell cycle. Stem cell factor (SCF), the ligand for the tyrosine kinase receptor c-kit, usually induces differentiation of the CD34-negative stem cells into CD34-positive haematopoietic precursors. SCF also suppresses the expression of c-myc-dependent Cyclin E, which is not transcribed initially, but expression occurs later on. Interleukin 6 (IL-6) instead rather promotes proliferation, but fails to induce proliferation in the majority of CD34-negative stem cells due to no STAT activation in quiescent cells. Nevertheless, the potential of quiescent D064 cells to proliferate eventually, becomes apparent by the low-level expression of IL-6 dependent STAT factors. D064 cells also spontaneously start to express Bax, while Bcl-2 is downregulated in parallel. In summary, CD34-negative haematopoietic stem cells dwell in the marrow or other niches as quiescent cells, until they can respond to autocrine or paracrine growth factor-mediated signals
AU  - Huss, R.*
AU  - Gatsios, P.*
AU  - Graeve, L.*
AU  - Lange, C.
AU  - Eissner, G.*
AU  - Kolb, H.-J.
AU  - Thalmeier, K.*
AU  - Heinrich, P.C.*
C1  - 21550
C2  - 19674
SP  - 1195-1204
TI  - Quiescence of CD34-Negative Haematopoietic Stem Cells is Mediated by Downregulation of Cyclin B and NO Stat Activation.
JO  - Cytokine
VL  - 12
IS  - 8
PY  - 2000
SN  - 1043-4666
ER  - 

TY  - JOUR
AB  - Injection of tumour necrosis factor (TNF) in animals causes severe liver cell toxicity, especially when D-(+)-galactosamine (GalN) is co-administered. After challenge with TNF/GalN, serum complement activity (CH50 and APCH50) decreased dramatically, suggesting strong activation of both the classical and the alternative pathways. TNF or GalN alone had no such effect. A cleavage product of complement protein C3 [C3(b)] was deposited on the surface of hepatocytes of TNF/GalN-treated mice. Intravenous administration of cobra venom factor (CVF), which depletes complement, inhibited the development of hepatitis. However, CVF pretreatment also protected C3-deficient mice. Pretreatment of mice with a C1q-depleting antibody did not prevent TNF/GalN lethality, although the anti-C1q antibody had depleted plasma C1q. Factor B-deficient and C3-deficient mice, generated by gene targeting, proved to be as sensitive to TNF/GalN as control mice. Furthermore, induction of lethal shock by platelet-activating factor, an important mediator in TNF-induced hepatic failure, was not reduced in C3-deficient mice. These data indicate that complement, although activated, plays no major role in the generation of acute lethal hepatic failure in this model and that CVF-induced protection is independent of complement depletion.
AU  - Libert, C.*
AU  - Wielockx, B.*
AU  - Grijalba, B.*
AU  - van Molle, W.*
AU  - Kremmer, E.
AU  - Colten, H.R.*
AU  - Fiers, W.*
AU  - Brouckaert, P.*
C1  - 21233
C2  - 19336
SP  - 617-625
TI  - The role of complement activation in tumour necrosis factor-induced lethal hepatitis.
JO  - Cytokine
VL  - 11
IS  - 8
PY  - 1999
SN  - 1043-4666
ER  -