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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

C57BL/6 mice were given intranasal instillation of optimal doses of the actinomycete Faeni rectivirgula 150 micrograms/mouse 3 days/wk), an important offending agent causing hypersensitivity pneumonitis. This instillation was associated with a very significant increase in the lung weight of the mice and also a large increase (10-fold) in the number of cells recovered from the bronchoalveolar lavage (BAL) of instilled mice. Also, this instillation was associated with a very significant fibrosis at 4 and 8 wk (2-fold increase in hydroxyproline levels in the lungs). We determined the effect of depleting certain T-cell subsets on the progression of this inflammatory disease. Elimination of the L3T4 subset did not significantly affect the increase in the lung index, the lung cellular influx, or its profile. Fibrosis was also unaffected by this depletion of L3T4+ cells. Similarly, depletion of Lyt2+ (CD8+) cells did not lead to significant changes in these disease parameters. Depletion of all T cells (Thyl+) was also ineffective at modifying the number of infiltrating cells and the lung index score. However, identification of cell types in BAL showed that mice depleted of Thyl+ cells had a cellular influx that was almost exclusively neutrophilic throughout the instillation period, whereas control mice developed only a transient neutrophilic response to F. rectivirgula instillation, which was replaced by a recruitment of mononuclear cells, mostly macrophages. Also, depletion of Thyl+ cells before and during F. rectivirgula challenge had no effect on tumor necrosis factor-alpha levels in the BAL of treated mice (63 +/- 13 U/ml in anti-Thy1. 2 antibodies treated versus 52 +/- 10 U/ml in the BAL of control mice given F. rectivirgula).(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Feb
PMID:T cells in hypersensitivity pneumonitis: effects of in vivo depletion of T cells in a mouse model. 154 Mar 81

Immunoreactive tumor necrosis factor-alpha (TNF-alpha) concentration is increased in plasma from patients with cystic fibrosis and chronic Pseudomonas aeruginosa pulmonary infection. To determine if circulating monocytes could be the source of plasma TNF-alpha, we determined in vitro basal and endotoxin-stimulated TNF-alpha secretion by monocytes. In 10 adult patients studied at the time of a symptomatic respiratory exacerbation, basal secretion of TNF-alpha was significantly less than that for 10 matched healthy controls (median 265 pg/micrograms DNA, nonparametric 95% confidence interval 193 to 463 pg/micrograms DNA versus 575, 298 to 923 pg/micrograms DNA; P less than 0.006), although both groups responded equally effectively to added Escherichia coli endotoxin at greater than or equal to 25 ng/ml. In six patients and six matched controls, monocyte culture was repeated after completion of 2 wk anti-pseudomonal antibiotic treatment in the patients. The reduced basal TNF-alpha secretion in the patients had reversed and was not significantly different to that of controls. This effect mirrored a significant reduction in plasma immunoreactive TNF-alpha in these patients (mean +/- SD, 258 +/- 59.3 pg/ml pretreatment versus 133 +/- 47.8 pg/ml post-treatment; P less than 0.05). These findings suggest that a reversible downregulation of TNF-alpha secretion occurred at the time of a symptomatic respiratory deterioration in the presence of chronic P. aeruginosa infection. This may represent a physiologic regulatory mechanism to maintain a local inflammatory response to chronic pulmonary infection in cystic fibrosis.
Am J Respir Cell Mol Biol 1992 Feb
PMID:In vitro tumor necrosis factor-alpha secretion by monocytes from patients with cystic fibrosis. 154 Mar 83

The pathogenesis of silicosis results, in part, from interactions between silica particles and alveolar macrophages (AM) with release of cytokines and other mediators. Different arachidonic acid metabolites have been shown to promote or to suppress inflammation and fibrosis. We designed experiments to study the production of cyclooxygenase metabolites and tumor necrosis factor-alpha (TNF-alpha) from macrophages during active silicosis. Macrophages were harvested from rats 5 to 7 mo after an 8-day silica aerosol exposure. Upon in vitro culture of AM, the spontaneous release of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and prostaglandin D2 (PGD2) of silica-exposed animals was higher than that of sham-exposed animals. Moreover, AM from silicotic rats displayed an increased sensitivity to low concentrations of lipopolysaccharide (LPS, 10 ng/ml) and released copious amounts of PGE2 and TXB2. When compared with similarly enhanced release of TNF-alpha from AM of silica-exposed rats, PGE2 production occurred later and started to increase when TNF-alpha production declined. Addition of the cyclooxygenase blocker indomethacin augmented TNF-alpha production, whereas the addition of PGE2 counteracted TNF-alpha release. Also peritoneal macrophages, which did not have direct contact with silica particles, released enhanced levels of PGE2 in response to low LPS doses. We conclude that AM and other macrophages from silica-exposed rats are preactivated and display an enhanced prostanoid production that could serve anti-inflammatory or immunomodulating roles in silicosis.
Am J Respir Cell Mol Biol 1992 Apr
PMID:Enhanced release of prostaglandin E2 from macrophages of rats with silicosis. 155 Jun 84

To evaluate the feasibility of tumor necrosis factor-alpha (TNF-alpha) treatment of lung cancer patients, we chose the malignant cells contained in their pleural effusions as a first convenient target. We found, however, that a TNF-alpha inhibitor (TNF-alpha I) activity was present in both patient sera and pleural fluids. We therefore compared the TNF-alpha I activity present in patients with benign or malignant pleural effusions using a bioassay of TNF-alpha inhibition and partially characterized it. A high TNF-alpha I activity characterizes cancer patients with sera levels twice as high as the control level measured for blood bank donors (2.54 +/- 1.28 versus 1.19 +/- 0.38) and with even higher levels in pleural fluids (3.75 +/- 1.83). In contrast, patients with benign pleural effusions present similar levels of TNF-alpha I activity, at about the control level, in both their sera and pleural fluids (1.37 +/- 0.98 versus 1.16 +/- 0.85). A high TNF-alpha I activity is consistently found in cancer patients but is only released in vitro by leukocytes. It is most likely related to recently purified TNF-alpha inhibitors that, as soluble shed fragments of TNF receptors, may function as traps for TNF molecules. This study suggests that tumors may evade TNF cytotoxic action by modulating systemic levels of TNF and implies a reassessment of TNF therapy in cancer patients.
Am J Respir Cell Mol Biol 1992 May
PMID:Characterization of a tumor necrosis factor-alpha inhibitor activity in cancer patients. 158 Oct 74

Various human alveolar macrophage (AM)-derived cytokines in the lungs have been shown to be present under conditions of normal homeostasis as well as during the pathogenesis of inflammation. Although extensive investigation has demonstrated the induction of cytokines from AM, relatively little is known regarding endogenous and exogenous regulation of their production. Several pharmacologic agents, including corticosteroids, cyclooxygenase inhibitors, prostaglandins, and methyl-xanthines have been examined for their role in the modulation of mononuclear phagocyte-derived cytokines. In this study, we examine the role of amiloride for the regulation of AM-derived interleukin (IL)-8, tumor necrosis factor (TNF), IL-6, and IL-1 beta. Amiloride in concentrations of 10(-4) to 10(-6) M, concentrations capable of being achieved in the distal airways via nebulization, were shown to inhibit lipopolysaccharide-stimulated, AM-derived IL-8 and TNF in both a time- and dose-dependent fashion. In addition, 5-(N,N-hexamethylene) amiloride hydrochloride, an amiloride analogue with specific sodium channel antiport inhibition, resulted in a similar dose-dependent suppression of lipopolysaccharide-stimulated, AM-derived IL-8 production. Furthermore, the suppressive effect of amiloride appeared to be at the level of mRNA for IL-8, TNF, IL-1 beta, and IL-6, whereas steady-state levels of beta-actin mRNA remained unaltered. These findings would suggest that amiloride has a potentially important modulating influence for the regulation of AM-derived cytokines.
Am J Respir Cell Mol Biol 1992 Jun
PMID:Suppression of human alveolar macrophage-derived cytokines by amiloride. 159 Oct 7

The antitumor activity of recombinant human tumor necrosis factor (rhTNF) against heterotransplanted human prostatic carcinoma (PC-3) and spontaneous lymphatic tumor metastasis was studied in vivo. The spontaneous lymphatic metastasis of PC-3 tumor was found in approximately 50% of cases. Significant antitumor activity was observed with repeated intratumoral administration of a large dose of rhTNF, not only on the subcutaneous tumor xenografts but also on the lymph node metastases. Strong antitumor activity could be achieved even with the intratumoral administration of a small dose of rhTNF in combination with mild hyperthermia on either the transplanted tumors or on the metastatic tumors.
Mol Biother 1992 Mar
PMID:Antitumor activity of recombinant human tumor necrosis factor in combination with hyperthermia against heterotransplanted human prostatic carcinoma and its lymph node metastasis in nude mice. 162 71

Clones encoding the type 1 (p80) and type 2 (p60) forms of the murine receptors for tumor necrosis factor (TNF) were isolated by cross-hybridization using probes derived from the cloned human TNF receptors. Each of the murine receptors shows strong sequence homology to the corresponding human receptor (approximately 65% amino acid identity) throughout the molecule but only modest homology, limited to ligand-binding domains, between themselves. The ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs: both receptor types bind TNF-alpha and -beta with multiple affinity classes, and the ligands cross-compete. Analysis of the murine transcripts encoding these receptors revealed the presence of RNAs for one or both forms of the receptors in all cells examined. It was also demonstrated that for both types of human TNF receptor, variably sized transcripts are observed in different cells. The murine cDNAs were further used to determine the chromosomal locations of the TNF receptor genes. They are not linked, in contrast to the ligands, and map to chromosomes 4 (type 1) and 6 (type 2).
Mol Cell Biol 1991 Jun
PMID:Molecular cloning and expression of the type 1 and type 2 murine receptors for tumor necrosis factor. 164 45

Previous work on the cytolytic action of activated macrophages indicated that tumor necrosis factor (TNF) showed synergistic cytolytic activity with NO, which has been shown to act as a cyclic GMP (cGMP) generator [Higuchi et al., J. Immun. 144, 1425-1431, (1990)]. In this study, we investigated the relationship between the accumulation of intracellular cGMP and the cytotoxic action of TNF. It was demonstrated that TNF-mediated cell lysis was closely related to the background level of intracellular cGMP, and that the accumulation of cGMP within TNF resistant cells induced TNF sensitivity. We reached these conclusions on the basis of the following results; (1) agents (sodium nitroprusside and isobutylmethylxantine) that cause the accumulation of cGMP intracellularly increased the TNF-sensitivity of TNF-resistant cells; (2) the addition of dibutyryl cGMP to TNF-resistant cells increased the TNF-sensitivity; and (3) treatment at 40 degrees C or agents such as interferon gamma and actinomycin D, that synergistically kill tumor cells together with TNF, potentially increased the cGMP level. Therefore, intracellular cGMP may be one of the key molecules that lead to cell death caused by TNF.
Mol Immunol 1991 Sep
PMID:TNF-mediated cytotoxicity. Importance of intracellular cGMP level for determining TNF-sensitivity. 165 46

Following our previous demonstration of cytokine secretion by alveolar macrophages (AM) from coal miners and from patients with coal workers' pneumoconiosis, we investigated the effect of in vitro exposure to coal dust and to its silica content on tumor necrosis factor-alpha (TNF), interleukin (IL)-1 beta, and IL-6 production by normal human AM. TNF and IL-1 beta concentrations were estimated by a specific radioimmunoassay, while IL-6 levels were evaluated by the proliferation of 7TD1 cells. After 24-h culture, coal dust triggered a significant release of TNF and IL-6 at the dose of 0.1 mg/ml and more obviously at 1 mg/ml in comparison with titanium dioxide (TiO2), used as a biologically inert control dust (with 1 mg/ml of dust: 3,526 +/- 3,509 versus 330 +/- 138 pg TNF/ml and 224 +/- 74 versus 72 +/- 34 U IL-6/ml, respectively; P less than 0.01 in both cases). After 3-h culture, a significant TNF secretion as well as an increased TNF mRNA expression were also detected for AM stimulated by coal dust at variance with TiO2. In contrast, no modification of IL-1 beta concentration could be evidenced in AM exposed to coal dust, although we detected an increased expression of specific mRNA expression. In order to define the role of silica among the main components of coal dust in AM activation, we evaluated the effect of silica (alpha-quartz, 30 micrograms/ml, which is the concentration and the type of silica present in our coal dust) alone or mixed with TiO2 (1 mg/ml) on monokine production.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Nov
PMID:Production of tumor necrosis factor-alpha and interleukin-6 by human alveolar macrophages exposed in vitro to coal mine dust. 165 62

The hypothalamus-pituitary-adrenal (HPA) axis is stimulated during the course of certain immune, inflammatory and neoplastic processes. IL-1 is an important immunologically derived cytokine mediating the stimulation of this axis, although not the only one. We have compared the relative potencies of the cytokines IL-1, IL-6 and tumor necrosis factor (TNF), which share several biological actions, for stimulating ACTH and corticosterone output in freely-moving rats. Although all three cytokines can stimulate the HPA axis, IL-1 was the most potent. This effect of IL-1 was also present during the neonatal period, when the response of the HPA axis to acute stress is reduced in rodents. The results support the existence of an immune-HPA axis circuit. The biological and clinical relevance of this circuit is discussed.
J Steroid Biochem Mol Biol 1991
PMID:Cytokines as modulators of the hypothalamus-pituitary-adrenal axis. 165 87


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