Neopterin activates transcription factor nuclear factor‐κB in vascular smooth muscle cells

Hoffmann, Georg; Schobersberger, Wolfgang; Frede, Stilla; Pelzer, Larissa; Fandrey, Joachim; Wächter, Helmut; Fuchs, Dietmar; Grote, J.

doi:10.1016/0014-5793(96)00729-6

Cited by 71 publications

(40 citation statements)

References 35 publications

(26 reference statements)

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“…Increased calprotectin levels have been detected in intestinal diseases associated with inflammation such as necrotizing enterocolitis, and its quantitation provides a measure of the degree of tissue inflammation in adults with irritable bowel disease (31,32). Neopterin and calprotectin appears to play a regulatory role in the inflammatory process as well as calprotectin (33,34). Calprotectin and neopterin expression by macrophages and monocytes depends on their differentiation status (28,29).…”

Section: Bowel Inflammation In Gastroschisismentioning

confidence: 99%

Biochemical Investigations of Bowel Inflammation in Gastroschisis

et al. 2006

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ABSTRACT:Neonates with gastroschisis have perivisceritis resulting from contact between the bowel and amniotic fluid. Here, we characterized the mediators involved in this inflammatory process in humans and ewes, to find a reliable marker of this process. We have diagnosed 41 cases of gastroschisis since 1995. Amniotic fluid sampled for karyotyping between 15 and 32 wk of gestation was also used to assay cytokines and inflammatory proteins. The findings were compared with those in 93 age-matched controls. Amniotic fluid cells were analyzed by means of cytology. Histologic examination of the bowel was performed when neonatal appendectomy was performed. The findings were compared with those obtained in a ewe model of gastroschisis. In gastroschisis, amniotic total protein, IL-6, IL-8, and ferritin levels were significantly higher than in controls. Gastroschisis was associated with significantly higher cell counts (mainly mononuclear cells) in amniotic fluid. At birth, macrophages were abundant in the fibrous peel covering the bowel. Similar results were obtained in the ewe model. Gastroschisis may be associated with a subchronic inflammatory process of variable intensity. This inflammation is restricted to the bowel wall and involves inflammatory cells such as macrophages, which may secrete ferritin, neopterin, and calprotectin. G astroschisis is an abdominal wall defect in which various segments of the bowel extrude through a small paraumbilical defect, usually situated on the right side. Prenatal diagnosis is usually made in the second trimester, when sonography shows bowel loops floating freely in amniotic fluid (1). Gastroschisis is rare (1/6000 to 1/10,000 pregnancies) and generally isolated. Its cause is unknown, but probably involves premature regression of the omphalomesenteric artery, leading to failure of the mesodermal components of the abdominal wall (2). The survival rate exceeds 90%. Factors of poor prognosis include intrauterine growth retardation, oligohydramnios, and the degree of perivisceritis at birth (3).Perivisceritis in this setting is due to aseptic peritonitis, probably secondary to prolonged exposure of the bowel to amniotic fluid (4). The components of amniotic fluid involved in this reaction are controversial, but we have previously obtained evidence incriminating high levels of digestive enzymes, which may aggress the gut; this is also supported by experimental findings (5,6). The inflammatory process includes edema, fibrin deposition, and cell infiltration of the bowel wall (7,8). We and Morrison et al. (9,10) have shown on restricted studies that the degree of inflammation should be used to evaluate gut damage. Here we studied a series of human cases of gastroschisis and used a ewe experimental model to examine the involvement of inflammatory cells and soluble mediators. MATERIALS AND METHODSPatients and samples. Forty-one human pregnancies complicated by fetal gastroschisis have been managed at Robert Debré Hospital since 1995. Gastroschisis was diagnosed between 15 and 32 wk of pre...

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Section: Bowel Inflammation In Gastroschisismentioning

confidence: 99%

Biochemical Investigations of Bowel Inflammation in Gastroschisis

et al. 2006

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“…Activation ofNF-K B by neopterin and 7,8-dihydroneopterin has been demonstrated earlier in cells from rats and humans (18,19). The engagement of this proliferative factor in the stimulation of CD34+ marrow stromal dendritic cells remains to be elucidated in further investigations.…”

Section: Discussionmentioning

confidence: 99%

Neopterin Acting as a Bone Marrow Stem Cell Factor on Early Common Haematopoietic (Myeloid) and Stromal (Dendritic, CD34+) Cell Progenitors in vitro

Zvetkova¹,

Fuchs²,

Katzarova³

et al. 2001

Pteridines

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The in vitro response of early haematopoietic progenitors or stem cells, common for myeloid (granulocyte, eosinophil, megacaryocyte) and marrow stromal (including dendritic CD34+) cells series, to neopterin, exogenously added to the liquid-and semi-liquid (agar-) mouse bone marrow cultures, at doses 12.5 -25 Jlg/ml culture medium, has been studied. The results obtained show a significant stimulation of common myeloid and stromal dendritic cell (CD34+) progenitors' proliferation and/or differentiation as early as 24h after the in vitro treatment of marrow cultures with neopterin. On day 4 of cultivation the granulocyte/macrophageal proliferation and differentiation has been attenuated giving place to the marrow stromal dendritic cell (probably CD34+) differentiation. The engagement of the nuclear proliferative factor NF-K B may playa role in the light of recent data that neopterin could activate this transcriptionally active nuclear factor. The significance of clonal selective stimulation of healthy (but not of leukaemic) dendritic CD34+ cells in some pathological cases as acute myeloid leukaemia has been also discussed because neopterin could be a more efficient marrow stem cell factor than cytokine cocktails with granulocyte/macrophage-colony stimulating factor. The ex vivo or clinical application of neopterin, alone and/or in specific combinations with other cytokines, in the induction of marrow myeloid and stromal cell proliferation and differentiation towards the dendritic (CD34+) cells merits further investigations ..

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“…in blood and organ donor screenings (19) Recent findings indicate that neopterin may be a part of the inflammatory arsenal of the body in response to infectious stimuli. Among other effects, neopterin was found to trigger inducible nitric oxide synthesis gene expression and nitric oxide release in vascular smooth muscle cells (VSMC) (20,21), to stimulate the generation of the pro-inflammatory cytokine tumor necrosis factor-α in VSMC (22), or to induce apoptotic cell death in VSMC and the alveolar type II-like epithelial cell line L2 (23,24). Most of these observations are based on long-term effects of neopterin requiring 12-24 h of incubation time.…”

Section: Discussionmentioning

confidence: 99%

Influence of Neopterin on Ciliary Beat Frequency of Human Nasal Epithelial Cells in vitro

Neher

Schobersberger²,

Augustijns³

et al. 2008

Pteridines

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Acute infectious diseases of the respiratory tract are regularly associated with increased concentrations of neopterin in serum and/or urine. Most likely, the pteridine compound is not only a marker of an activated cellular immune system but may exert distinct biochemical functions in the process of infections as well. In response to viral contact, macrophages located in the nasal mucosa may represent a source for neopterin in the nasal cavity with potential hazardous effects on ciliary beat frequency (CBF), thus promoting chronic infectious processes. The aim of the present study was to investigate the effects of neopterin at different concentrations (10 nM, 100 nM, and 100 µM) on CBF in human nasal epithelial cells in vitro. Samples were taken from the inferior nasal turbinate and incubated with neopterin dissolved in either aqua destillata or in sodium chloride (0.9%) at the given amounts for 2, 5, 10, and 20 min. In a preliminary set of experiments, neopterin inhibited CBF following the 5 and 10 min. incubation protocol, respectively. However, analyses of pooled data from 28 experiments using sodium chloride (0.9%) as solvent could not confirm these findings: in no setting a significant reduction of CBF was detected at the end of the 20 min. experimental procedure. Therefore, we conclude that neopterin most likely does not affect the mucociliary clearance defense mechanisms in the course of infections of the nasal respiratory tract.

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Neopterin activates transcription factor nuclear factor‐κB in vascular smooth muscle cells

Cited by 71 publications

References 35 publications

Biochemical Investigations of Bowel Inflammation in Gastroschisis

Biochemical Investigations of Bowel Inflammation in Gastroschisis

Neopterin Acting as a Bone Marrow Stem Cell Factor on Early Common Haematopoietic (Myeloid) and Stromal (Dendritic, CD34+) Cell Progenitors in vitro

Influence of Neopterin on Ciliary Beat Frequency of Human Nasal Epithelial Cells in vitro

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