Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenomedullin, originally discovered from pheochromocytoma, is a member of the calcitonin gene-related peptide family. The production and secretion of adrenomedullin by cultured human astrocytes were studied by northern blot analysis and radioimmunoassay. Northern blot analysis showed the expression of adrenomedullin mRNA in cultured human astrocytes. Immunoreactive adrenomedullin concentrations in the culture medium were 29.6+/-1.2 fmol/10(5) cells/24 h (mean +/- SEM, n = 4). Treatment with interferon-gamma (100 U/ml), tumor necrosis factor-alpha (1 and 10 ng/ml), or interleukin-1beta (1 and 10 ng/ml) for 24 h caused >20-fold increases in immunoreactive adrenomedullin levels in the culture medium of human astrocytes. On the other hand, northern blot analysis showed only small increases (approximately 40%) in the adrenomedullin mRNA expression of human astrocytes with either 100 U/ml interferon-gamma or 10 ng/ml interleukin-1beta and no noticeable change with tumor necrosis factor-alpha. Reverse phase HPLC of the medium extracts of human astrocytes treated with interferon-gamma, tumor necrosis factor-alpha, or interleukin-1beta showed that most of immunoreactive adrenomedullin was eluted in the position of adrenomedullin-(1-52). On the other hand, immunoreactive adrenomedullin in the medium of human astrocytes without cytokine treatment was eluted earlier than the adrenomedullin standard, suggesting that this immunoreactive adrenomedullin represents adrenomedullin with some modifications or fragments of the adrenomedullin precursor. The present study has shown the production and secretion of adrenomedullin by human astrocytes and increased secretion of adrenomedullin by cytokines.
 ...
PMID:Increased secretion of adrenomedullin from cultured human astrocytes by cytokines. 1061 10

Atopic dermatitis (AD) is associated with increased IL-4, IL-5, and IL-13 but decreased IFN-gamma production. This cytokine profile may account for the atopic features of this illness, including IgE upregulation. Recent studies have demonstrated that tumor necrosis factor (TNF)-beta is produced by Th1-like cells, but the cytokine modulation by TNF-beta and the clinical significance of this cytokine in AD is not known. Therefore, this study was carried out to determine the potential role of TNF-beta in AD. In this study, we cultured peripheral blood mononuclear cells from patients with AD and normal subjects with anti-CD3 monoclonal antibodies and investigated the production of TNF-beta by ELISA. The mean +/- SEM of TNF-beta production in AD was significantly lower than normal subjects (p = 0.03). The effect of TNF-beta on cytokine production was investigated by culturing peripheral blood mononuclear cells with anti-CD3 monoclonal antibodies in the presence or absence of TNF-beta. Compared with medium control, TNF-beta significantly decreased IL-5 (p = 0.0004) and IL-13 (p = 0.008) but increased IFN-gamma (p = 0.001) production. The effect of TNF-beta on IgE production was determined by culturing peripheral blood mononuclear cells in the IL-4- and anti-CD40-induced IgE production system. Interestingly, TNF-beta significantly decreased IgE (p = 0.02), but not IgG production compared with medium control. Our study demonstrates that TNF-beta production is downregulated in AD. This cytokine increases IFN-gamma production but decreases IL-5, IL-13, as well as IgE production. These findings suggest a potential role for TNF-beta in the pathogenesis of AD.
 ...
PMID:The modulation of cytokine and IgE production by tumor necrosis factor-beta in atopic dermatitis. 1062 Jan 39

The production and secretion of peptides by adrenocortical tumors have not been well studied. We therefore studied the production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1 in SW-13 human adrenocortical carcinoma cells by radioimmunoassay and Northern blot analysis. Both immunoreactive-adrenomedullin and immunoreactive-endothelin were detected in the culture medium of SW-13 cells (27.7 +/- 1.6 fmol/10 (5) cells/24 h and 11.0 +/- 0.8 fmol/10 (5) cells/24 h, respectively, mean +/- SEM, n = 6). Northern blot analysis showed the expression of adrenomedullin mRNA and endothelin-1 mRNA in SW-13 cells. On the other hand, no significant amount of calcitonin gene-related peptide, corticotropin-releasing hormone, neuropeptide Y, or urocortin was secreted by SW-13 cells. Treatment with ACTH (10(-9)-10(-7) mol/l), angiotensin II (10(-9)-10(-7) mol/l), or dexamethasone (10(-8)-10(-6) mol/l) for 24 h had no significant effects on immunoreactive-adrenomedullin levels and immunoreactive-endothelin levels in the culture medium of SW-13. Treatment with tumor necrosis factor (TNF)-alpha (20 ng/ml) increased significantly both immunoreactive-adrenomedullin levels and immunoreactive-endothelin levels in the culture medium. Interferon-gamma (100 U/ml) increased the immunoreactive-endothelin levels, but not immunoreactive-adrenomedullin levels, whereas interleukin-1 (IL-1)beta (10 ng/ml) increased immunoreactive-adrenomedullin levels, but not immunoreactive-endothelin levels. These findings indicate that SW-13 human adrenocortical carcinoma cells produce and secrete two vasoactive peptides, adrenomedullin, and endothelin-1 and that the secretion of these two peptides is modulated differently by cytokines.
 ...
PMID:Production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1, by cultured human adrenocortical carcinoma cells. 1076 53

Taking into account that cytokine tumor necrosis factor-alpha (TNF-alpha) and mast cells (MC) both are involved in inflammation, it seems of great importance to recognize their relationships. Therefore, we have studied whether recombinant human TNF-alpha (rHuTNF-alpha) can cause histamine secretion from rat peritoneal MC. We have also examined the effect of this cytokine on MC reactivity. We have established that TNF-alpha stimulates rat MC to histamine release in a concentration-dependent manner. TNF-alpha-induced histamine secretion was evoked by concentrations > 10-16 M and reached the maximum rate at a concentration of 10-10 M (histamine release 17.1% +/- 1.9%, mean +/- SEM). We have also noticed that pretreatment of MC with TNF-alpha (in a concentration of 10-16 M) significantly inhibited concanavalin A (ConA)-stimulated release of histamine, with the percent release decreasing to 51% of the control value. Treatment of mast cells with TNF-alpha resulted in a decrease of compound 48/80-dependent histamine release as well (the percent released histamine fell to 85% of the control value). This altered MC responsiveness was reversible. After 120 min of resting time, the MC reactivity came back to the initial values. We have concluded that TNF-alpha appears to be a direct stimulus for MC to release histamine, and it may regulate MC secretory function.
 ...
PMID:The action of tumor necrosis factor-alpha on rat mast cells. 1080 72

Low bone density, fractures, and kyphosis complicate the lives of adults with cystic fibrosis (CF), and inflammatory cytokines (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha) that may alter bone metabolism have been previously found to be increased in the lungs and serum of CF patients. The objective of this prospective study was to determine the impact of lung infection on bone physiology in 17 adult CF patients. Serum osteocalcin, a marker of bone formation; urine N-telopeptides of type I collagen and free deoxypyridinoline, both of which are markers of bone breakdown; serum cytokines (TNF-alpha, IL-1beta, and IL-6); and general inflammatory markers (serum C-reactive protein [CRP] and chondrex) were measured at the beginning and end of treatment for an acute exacerbation of lung infection and again 3 wk later. After treatment with conventional antibiotics, decreases in N-telopeptides (147.3 +/- 77.5 [mean +/- SEM] versus 95.5 +/- 57.3 bone collagen equivalents (BCE)/mmol creatinine, p = 0.0014), deoxypyridinoline (8.42 +/- 2.8 versus 6.8 +/- 3.0 mmol/mmol creatinine, p = 0.08), IL-1beta (1.43 +/- 1.13 versus 0.65 +/- 0.63 pg/ml, p = 0.03), IL-6 (9.5 +/- 6.5 versus 4.7 +/- 3.2 pg/ml, p = 0. 012), CRP (43.1 +/- 29.3 versus 23.4 +/- 25.3 mg/ml, p = 0.04), and chondrex (151.7 +/- 111.7 versus 101.4 +/- 67.3 ng/ml, p = 0.014), and increases in osteocalcin levels (14.5 +/- 5.4 versus 22.5 +/- 8. 7 ng/ml, p = 0.010) were observed. Three weeks later, the changes in N-telopeptides and osteocalcin persisted. These data indicate that pulmonary infection, through the elaboration of inflammatory cytokines, may be linked to increased bone resorption and diminished bone formation. These results provide insights into the impact of systemic inflammation on bone health, and suggest novel mechanisms for bone disease in CF.
 ...
PMID:Adverse alterations in bone metabolism are associated with lung infection in adults with cystic fibrosis. 1106 95

Mechanisms by which immunodepressants (Cyclosporine, CsA; FK 506, FK; Azanthioprine, AZA) ameliorate warm ischemic injury of the liver were examined. Female Sprague-Dawley rats were subjected to 60-min of normothermic liver ischemia. Animals were assigned to one of four groups: group I, control with vehicle treatment; groups II, III, and IV, treatment with CsA (10 mg/kg), FK (1 mg/kg), and AZA (1 mg/kg), respectively. The immunosuppressive agents were given per os for 4 consecutive days prior to the induction of hepatic ischemia. In addition to a survival study, plasma levels of endotoxin, serum activities of tumor necrosis factor-alpha (TNF), plasma levels of phosphatidylcholine hydroperoxide (PCOOH) as a lipid peroxide, and serum alanine aminotransferase (ALT) were investigated in blood samples collected from the suprahepatic vena cava. A 7-day survival period was significantly higher in the immunosuppressed animals. Serum TNF levels were elevated and peaked at 3 h following reperfusion. When, the peak values were compared, the animals given immunodepressants had significantly lower levels of TNF (217.0 +/- 40.6 pg/ml for group I, 67.6 +/- 13.7 for group II, 87.9 +/- 28.3 for group III and 89.1 +/- 19.9 for group IV; Mean +/- SEM). Plasma PCOOH levels were also elevated following reperfusion, but with no statistical difference among the groups. Our data suggest that immunodepressants ameliorate warm ischemia/reperfusion injury through modulation of TNF production and not through a diminution of lipid peroxidative injury.
 ...
PMID:Immunodepressants ameliorate normothermic ischemia injury to the rat liver by down-regulating tumor necrosis factor, not by alleviation of lipid peroxidative injury. 1127 Dec 94

To determine whether macrolide antibiotics improve pulmonary function and decrease airway inflammation in cystic fibrosis (CF), we treated 10 patients (females; aged 19-26 years, all colonized with P. aeruginosa, none with atypical Mycobacteria) with 3 weeks of placebo, followed by 6 weeks of clarithromycin (500 mg BID) in a single-blind prospective study. We also determined the safety of sputum induction and the reproducibility of assessing inflammatory markers in induced sputum. Subjects performed spirometry and underwent sputum induction (12-min inhalation of 3% saline) at 3-week intervals. We found that sputum induction was well-tolerated. We also found that the reproducibility was high for neutrophil (PMN) number (R = 0.87, P = 0.009), interleukin (IL)-8 (R = 0.73, P < 0.05, free neutrophil elastase (NE) (R = 0.82, P < 0.05), and myeloperoxidase (MPO) levels (R = 0.86, P < 0.05), but was less so for tumor necrosis factor (TNF)-alpha (R = -0.15, P = 0.7). We found no significant difference in pulmonary function after 6 weeks of treatment with clarithromycin (FEV(1) (% predicted) (mean +/- SEM), 2.2 +/- 0.9 (60 +/- 24%) vs. 2.3 +/- 1 (61 +/- 29%)), and no significant differences in any of the inflammatory indices measured. The median (and range) values before and after treatment for indices of airway inflammation in the induced sputum samples were: for PMNs, 8 (1-326) and 21 (0.2 -175) x 10(6) cells/mL sputum; for IL-8, 156 (24-656) and 202 (16-680) ng/mL; for free NE, 260 (31-1,264) and 237 (49-1,048) microg/mL; for TNF-alpha, 20 (7-128) and 35 (17-87) pg/mL; and for MPO, 169 (13-960) and 195 (14-816) microg/mL. We conclude that clarithromycin is not uniformly effective in improving airway obstruction or in decreasing airway inflammation in patients with CF.
 ...
PMID:Effect of clarithromycin on airway obstruction and inflammatory markers in induced sputum in cystic fibrosis: a pilot study. 1141 73

The relationship between monocyte immune responses and cognitive impairment during progressive human immunodeficiency virus type 1 (HIV-1) infection was investigated in 28 subjects receiving highly active antiretroviral therapy. The mean+/-SEM CD4(+) T lymphocyte count and virus load for all patients were 237+/-41 cells/mm(3) and 77,091+/-195,372 HIV-1 RNA copies/mL, respectively. Levels of soluble tumor necrosis factor-alpha type II receptor (sTNF-RII) and soluble CD14 (sCD14) were measured in plasma by ELISA and were correlated with results from neuropsychological, magnetic resonance imaging, and magnetic resonance spectroscopy tests. Plasma sCD14 and sTNF-RII levels were elevated in subjects with cognitive impairment and in those with brain atrophy. Furthermore, both factors were correlated with spectroscopic choline:creatine ratios. These findings support the idea that peripheral immune responses are linked to cognitive dysfunction during advanced HIV-1 disease.
 ...
PMID:Plasma levels of soluble CD14 and tumor necrosis factor-alpha type II receptor correlate with cognitive dysfunction during human immunodeficiency virus type 1 infection. 1151 30

Constitutive mRNA expression and secretion of proinflammatory and anti-inflammatory cytokines was comparatively analyzed in rheumatoid arthritis (RA) synovial fibroblasts (SFB), isolated from primary culture or derived by repeated passage; normal-skin fibroblasts were used as controls. First-passage RA-SFB (n = 3) secreted large amounts of IL-6 (15,800 +/- 2,110 pg/ml; mean +/- SEM), but only limited amounts of tumor necrosis factor (TNF)-alpha (22.1 +/- 1.1 pg/ml) or IL-10 (35.7 +/- 34.2 pg/ml; only one of three samples was positive). IL-1beta, IL-15, and IL-18 were not detectable at the protein level and showed very low mRNA levels by semiquantitative RT-PCR. In repeated-passage RA-SFB (tenth passage), protein secretion was significantly lower for IL-6 (one-twentieth of the initial level) and TNF-alpha (two-thirds), and markedly reduced for IL-10 (one-quarter, with only one of three samples positive). While the decrease of IL-10 protein from first to tenth passage was paralleled by a corresponding decrease of mRNA, the relative mRNA levels for IL-6 and TNF-alpha were actually increased (20-fold and 300-fold, respectively), indicating post-transcriptional and/or post-translational regulation of these cytokines. Due to highly variable levels among individual patients, however, no significant differences were observed for any cytokine mRNA between primary-culture and repeated-passage RA-SFB (ninth passage). Likewise, no significant differences were detectable between RA-SFB and normal-skin fibroblasts (primary-culture and repeated-passage). By producing high amounts of IL-6 and limited amounts of TNF-alpha, RA-SFB may contribute to the (im)balance of proinflammatory and anti-inflammatory cytokines in the inflamed joint.
 ...
PMID:Cytokine mRNA and protein expression in primary-culture and repeated-passage synovial fibroblasts from patients with rheumatoid arthritis. 1187 47

Bacterial endotoxin activity is elevated in patients with decompensated chronic heart failure (HF) and acts as a potent stimulus for immune activation. We sought to determine whether endotoxin, at an activity level seen in vivo (around 0.6 EU/ml), is sufficient to stimulate the secretion of tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha soluble receptor (sTNFR2) in ex vivo whole blood from patients with HF. We studied 15 patients with HF (aged 65 +/- 1.9 years, New York Heart Association class 2.1 +/- 0.3, left ventricular ejection fraction 31 +/- 5%; mean +/- SEM), of whom 5 had cardiac cachexia, and 7 healthy control subjects (59 +/- 5 years, p = NS). Reference endotoxin was added to venous blood at concentrations of 0.6, 1.0, and 3.0 EU/ml, and was incubated for 6 hours. Endotoxin induced a dose-dependent increase in TNF-alpha release (p <0.05 in all groups). Patients with noncachectic HF produced significantly more TNF-alpha compared with controls after stimulation with 0.6, 1.0, and 3.0 EU/ml of endotoxin (113 +/- 46 vs 22 +/- 4 [p = 0.009], 149 +/- 48 vs 34 +/- 4 [p = 0.002], and 328 +/- 88 vs 89 +/- 16 pg/ml [p = 0.002], respectively; mean +/- SEM). Patients with cardiac cachexia produced significantly less TNF-alpha compared with patients without cardiac cachexia for all given concentrations (all p <0.05, analysis of variance p = 0.02). Production of sTNFR2 was greater at all concentrations of endotoxin versus controls (all p <0.05, analysis of variance p = 0.002). Plasma endotoxin levels were higher in patients with cardiac cachexia (4.3 times higher than in control subjects, p <0.005). Thus, low endotoxin activity, at levels seen in vivo in patients with HF, induces significant TNF-alpha and sTNFR2 production ex vivo. These results suggest that elevated plasma endotoxin activity observed in patients with HF is of pathophysiologic relevance.
 ...
PMID:Pathophysiologic quantities of endotoxin-induced tumor necrosis factor-alpha release in whole blood from patients with chronic heart failure. 1245 Jun 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>