Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor-alpha (TNF-alpha) has been implicated as an important mediator in the development of multiple system organ failure after either severe injury or infection. Using the rat cremaster muscle, we previously showed that systemically administered TNF-alpha caused hypotension, tachypnea, and microvascular protein leakage in association with leukocyte-endothelial adherence. In the current study, we hypothesized that topical administration of TNF-alpha to the cremaster muscle would cause microvascular protein leakage independent of changes in hemodynamic parameters. In addition, histological methods were used to study the role of neutrophils and mast cells in the TNF-alpha-induced microvascular protein leakage. Topically applied low-dose (1 ng/ml) TNF-alpha caused microvascular leakage in the cremaster, without changes in central hemodynamic parameters, but high-dose TNF-alpha (10 ng/ml) did not cause protein leakage. Histological studies did not demonstrate evidence of either neutrophil adhesion or mast cell degranulation in topically applied TNF-alpha-treated cremasters compared to controls. These data suggest that TNF-alpha-induced macromolecular leakage is a dose-dependent phenomenon which can occur independently of neutrophils or mast cell degranulation.
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PMID:Tumor necrosis factor causes microvascular protein leakage independently of neutrophils or mast cells. 801

Tumor necrosis factor-alpha production and products of mast cell, basophil, and eosinophil degranulation (prostaglandin D2, histamine, and eosinophil cationic protein) were prospectively studied in 26 children undergoing cardiac operations. The relationship between inflammatory response to cardiopulmonary bypass and transient postoperative arrhythmias was analyzed. Cardiopulmonary bypass was conducted with circulatory arrest and deep hypothermia in 10 patients and with continuous low-flow and moderate hypothermia in 16 patients. Transient postoperative arrhythmias diagnosed on standard or atrial electrocardiograms (or both) were seen in eight of the 26 examined children: accelerated junctional rhythm (n = 3), junctional ectopic tachycardia (n = 3), second-degree atrioventricular block (n = 1), and third-degree atrioventricular block (n = 1). Children with transient postoperative arrhythmias were younger than those without (p < 0.05). Compared with baseline values, there was in all patients a significant release of histamine and eosinophil cationic protein (p < 0.05) related to cardiopulmonary bypass, reaching peak values 4 hours after the operation. In contrast, tumor necrosis factor-alpha production and prostaglandin D2 release were not significant. This suggests that activated basophils but not mast cells are the major sources of histamine liberated during and after cardiopulmonary bypass. Histamine release but not eosinophil cationic protein release correlated with circulatory arrest and deep hypothermia (p < 0.05), suggesting the participation of physicochemical alterations of circulating basophils leading to histamine liberation. Four hours after the operation, patients with transient postoperative arrhythmias had significantly higher blood concentrations of histamine (p < 0.02) and eosinophil cationic protein (p < 0.05) than did those without transient postoperative arrhythmias. On the first postoperative day, four of the eight patients with transient postoperative arrhythmias had persisting elevated histamine levels, whereas in patients without transient postoperative arrhythmias histamine reached baseline values. The multivariate analysis retained histamine release and eosinophil cationic protein variations related to cardiopulmonary bypass for the emerging model to predict transient postoperative arrhythmias. The results of this study show significant histamine release related to cardiopulmonary bypass. Furthermore, they document a possible relationship between circulating histamine and transient postoperative arrhythmias. The latter may therefore be suspected among the consequences of the inflammatory response to cardiopulmonary bypass.
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PMID:Histamine liberation related to cardiopulmonary bypass in children: possible relation to transient postoperative arrhythmias. 862 22

Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm), showing alopecia, epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To further elucidate its pathogenesis, organs of 1-, 2-, 3-, 4-, 5-, and 6-week-old cpdm/cpdm mice were examined. At 4 weeks, the epidermal thickness was increased, whereas already at 3 weeks, the bromodeoxyuridine incorporation was increased in the basal keratinocytes. However, already at the age of 1 week, skin, lungs, and lymph nodes were infiltrated by eosinophils although no macroscopic lesions were present. Compared with control animals, 6-week-old cpdm/cpdm mice had decreased serum IgE levels and increased numbers of mast cells. From the age of 1 week these mast cells became increasingly IgE positive. In contrast, the mast cells of the control animals remained IgE negative. Mast cells of control and cpdm/cpdm mice were interleukin-4 and tumor necrosis factor-alpha positive. A likely explanation for the tissue infiltration of eosinophils could be the release of interleukin-4 and tumor necrosis factor-alpha from activated mast cells. Tumor necrosis factor-alpha may lead to the expression of E-selectin on endothelial cells, facilitating interleukin-4-mediated eosinophil transendothelial migration. Although various pathogenetic aspects of the cpdm/cpdm mouse need further elucidation, this model can be a tool to study eosinophil infiltration, leukocyte-endothelial cell interactions, and mast cell proliferation. Furthermore, the cpdm/cpdm mouse can be used to study chronic inflammatory skin disease because of the severe epidermal proliferation.
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PMID:Pathogenesis of skin lesions in mice with chronic proliferative dermatitis (cpdm/cpdm). 877 48

Unregulated increasing of Tumor necrosis factor-alpha (TNF-alpha) could be pathogenic in inflammatory diseases. The aim of this study was to investigate the anti-inflammatory role of the Substance P-antagonists (SPAs) through the inhibition of histamine release (HR) and TNF-alpha production from mast cell. Rat peritoneal mast cells (PMC) stimulated with Substance P (SP), in the presence of SPAs or not, were analyzed for HR and TNF-alpha protein production. Competitive Polymerase Chain Reaction, with an internal standard competing with target cDNA for the same primers, was used to determine the TNF-alpha mRNA expression. We show that the increase of either HR and TNF-alpha levels in peritoneal (PMC) after induction with SP was inhibited by pre-incubation with SPA or with the Peptide 101 (P101), while the [D-Pro2, D-Phe7, D-Trp9]-SP (dSP) had no effect. Neuraminidase treatment suggests that dSP, as well as SP, interacts with sialic acid residues on the cell surface. Moreover, SPA and P101 also inhibit the release of histamine and TNF-alpha induced by dSP suggesting that a receptor-independent mechanism is involved. These data could be useful to better understand the mechanisms involved in the mast cell activation and TNF-alpha production in the inflammatory diseases where SP is involved.
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PMID:Mast cell production of TNF-alpha induced by substance P evidence for a modulatory role of substance P-antagonists. 1058 Jul 96

Histamine-releasing antibodies that act against the epitope of the alpha chain of Fc(epsilon)RI (anti-Fc(epsilon)RI(alpha) antibody) that may affect pathogenesis in serum of patients with chronic urticaria. We assessed the capability of anti-Fc(epsilon)RI(alpha) antibody in sera from patients with chronic urticaria to release histamine and cytokines, and to induce the expression of endothelial cell adhesion molecules. We also assessed the release of inflammatory mediators from cultured foreskin mast cells, and expression of endothelial cell adhesion molecules on human dermal microvascular endothelial cells. Cells were pretreated with mast cell-conditioned media: culture media of mast cells treated with sera from chronic urticaria patients containing anti-Fc(epsilon)RI(alpha) antibody. Histamine release from human foreskin mast cells challenged with sera, increased after both 20 min and 16 h intervals. Leukotriene D4 release also increased at both 20 min and 16 h. Tumor necrosis factor-alpha increased significantly in foreskin mast cell culture challenged with sera of chronic urticaria patients. After the stimulation of human dermal microvascular endothelial cells with the conditioned media, the expression of intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin increased significantly. Treatment of the conditioned media with anti-tumor necrosis factor-alpha monoclonal antibody partially inhibited the expression of intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. The data suggest that sera from patients with chronic urticaria containing anti-Fc(epsilon)RI(alpha) antibody release mediators and tumor necrosis factor-alpha by activating human foreskin mast cells. This release can play a pathogenic role in chronic urticaria by activating endothelial cells, in part due to the actions of tumor necrosis factor-alpha from mast cells.
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PMID:Increased expression of endothelial cell adhesion molecules due to mediator release from human foreskin mast cells stimulated by autoantibodies in chronic urticaria sera. 1191 13

Tumor necrosis factor-alpha (TNFalpha) is presumably shed from cell membranes by TNFalpha-cleaving enzyme (TACE). The peptides SPLAQAVRSSSR and Dabcyl-LAQAVRSSSR-Edans, each encompassing the cleavage sequence of pro-TNFalpha recognized by TACE, were applied to intact umbilical vein endothelium (HUVEC), peripheral blood leukocytes (PBL) and the mast cell line HMC-1, which express TACE, to homogenates of rat heart tissue and to membrane and cytoplasmic extracts of PBL. Formation of SPLAQA (specific cleavage) was determined by HPLC, while cleavage (specific plus non-specific) of Dabcyl-TNFalpha-Edans was followed over time by measuring fluorescence. Participation of TACE was assessed from inhibition due to the drug TAPI-2. Incubation with recombinant human TACE gave specific cleavage, fully inhibitable by TAPI-2 (IC50 < 0.1 microM). HUVEC rapidly degraded TNFalpha-peptide, but in a non-specific manner (no SPLAQA detectable) and 50 microM TAPI-2 was without effect. Fluorescence was evoked when Dabcyl-LAQAVRSSSR-Edans was incubated with HMC-1 or PBL and also with cytoplasmic and membrane fractions of lysed PBL, but in no case was there significant inhibition by TAPI-2. However, marginal (10%) inhibition of fluorescence by 50 microM TAPI-2 was observed with homogenized heart tissue. This contained TACE, about 75% of which was without the inhibitory cysteine switch (Western blot). In conclusion, simple peptide analogs of pro-TNFalpha cannot be employed as substrates for measuring membrane TACE activity, largely due to extensive non-specific proteolytic cleavage by whole cells and cell extracts.
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PMID:Application of peptides containing the cleavage sequence of pro-TNFalpha in assessing TACE activity of whole cells. 1253 May 49

A mouse model of burn injury demonstrates increasing mortality to an infectious challenge in the form of cecal ligation and puncture (CLP) reaching a peak at 10 days after injury. Because it is widely believed that peritoneal mast cells play an important role in the defense against peritoneal sepsis, we wished to explore the possibility that peritoneal mast cell dysfunction contributed to increased CLP mortality after burn injury. Kit(W-v) C57BL/6 mice, which were shown to lack peritoneal mast cells by cytospin and flow cytometry, and normal littermate control animals were subjected to 25% burn or sham burn injury and 10 days later underwent CLP. Burn injured Kit(W-v) and normal littermates had a high CLP mortality when compared with sham-injured Kit(W-v) and normal littermates (P < 0.003), but the sham- and burn-injured Kit(W-v) and normal littermate animals did not differ from one another with respect to CLP mortality. This result prompted a comparison of CLP mortality in untreated WBB6F1 Kit(W/W-v) mice, known to be mast cell deficient, and normal littermate controls, as well as untreated C57BL/6 Kit(W-v) and normal littermates. The WBB6F1 Kit(W/W-v) mice showed significantly increased mortality after CLP as compared with the littermate controls (P = 0.03), whereas both C57BL/6 Kit(W-v) and littermate controls had very low mortality after CLP. A study of peritoneal cell populations 24 h after CLP failed to reveal an obvious cause for the difference in CLP survival between the two mast cell-deficient strains. Tumor necrosis factor-alpha (TNF-alpha) measurements in peritoneal fluid showed appreciable amounts of TNF-alpha in the littermate controls of both strains and little in the fluid obtained from the mast cell-deficient animals of both strains. We conclude that peritoneal mast cell dysfunction is unlikely to be a major cause of decreased resistance to peritoneal sepsis in burn-injured animals and that the importance of peritoneal mast cells in combating peritoneal sepsis in the mouse appears to be strain dependent.
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PMID:Mast cells and resistance to peritoneal sepsis after burn injury. 1278 5

Tumor necrosis factor-alpha (TNF-alpha) is released from activated mast cells via an IgE-dependent mechanisms, and plays a crucial role in ocular allergic inflammation. This study examined the influence of three antiglaucoma drugs differing in their chemical structure and pharmacological profile (i.e. latanoprost, timolol, GLC756) on TNF-alpha release from activated rat mast cells. A rat basophilic leukemia mast cell line (RBL-2H3) was activated via IgE/anti-IgE. Rat mast cells were incubated with latanoprost, timolol, GLC756 or betamethasone (positive control) at concentrations of 0.1, 1, 10 and 30 microM. TNF-alpha concentration in supernatant was measured by ELISA 5 h post-activation. Compared to controls, the prostaglandin derivative latanoprost and the beta-blocker timolol in the concentration range 0.1-30 microM, had no significant effect on TNF-alpha release from rat mast cells measured 5h after activation. By contrast, the dopaminergic drug GLC756 compared to controls in the concentration range 1-30 microM significantly inhibited TNF-alpha release from activated rat mast cells in a concentration-dependent manner. The positive control betamethasone inhibited TNF-alpha release almost completely at all concentrations tested. In conclusion, the results of this study suggest that latanoprost and timolol do not reduce inflammation triggered by activated mast cells. By contrast, the dopaminergic drug GLC756 inhibited TNF-alpha release from activated mast cells, suggesting an palliative potential of dopaminergic compounds on allergic conjunctivitis in topical glaucoma medication.
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PMID:Effect of GLC756, a novel mixed dopamine D1 receptor antagonist and dopamine D2 receptor agonist, on TNF-alpha release in vitro from activated rat mast cells. 1696 72

Schisandra fructus has been used for treatment of cough and thirst in Korea. However, its therapeutic mechanisms remain largely unclear. To investigate the biological effect of Schisandra fructus water extract (SFWE), we examined the effect of SFWE on the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-induced pro-inflammatory cytokine secretion in the human mast cell line HMC-1. HMC-1 cells were stimulated with PMA plus A23187 in the presence or absence of SFWE. Tumor necrosis factor (TNF)-alpha, interleukin 6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) productions were measured by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction. Inhibitory IkappaB/nuclear factor-kappaB (NF-kappaB) expression was assessed by western blot. SFWE suppressed PMA plus A23187-induced TNF-alpha, IL-6, and GM-CSF production in dose-dependent manners. Furthermore, SFWE inhibited IkappaB degradation and NF-kappaB nuclear translocation. These results suggest that SFWE inhibits the secretion of pro-inflammatory cytokines in HMC-1 cells through blockade of IkappaB degradation and NF-kappaB activation. Taken together, these findings may help elucidate the mechanism of action of this medicine in the modulation of mast cell activation in inflammatory conditions.
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PMID:Effects of the Schisandra fructus water extract on cytokine release from a human mast cell line. 1720 33

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which preferentially induces apoptosis in cells that have undergone malignant transformation. In humans, non-neoplastic cells are normally protected from the effects of TRAIL by expressing decoy receptors, lacking death domains. In contrast, neoplastic cells tend to downregulate their decoy receptor expression, increasing their susceptibility to the pro-apoptotic effects of TRAIL, via the functional TRAIL receptors. The aim of the current study was to investigate the effect of TRAIL on the canine C2 mastocytoma cell line to determine whether this agent might be a suitable treatment for mast cell tumors in dogs. C2 and MDCK cells were cultured with recombinant human TRAIL. Apoptosis was assessed using a Caspase 3 and 7 chemiluminescence assay and flow cytometry following Annexin V:FITC labelling. Cell metabolism was assessed using a colorimetric MTT-based assay. C2 cells demonstrated greater sensitivity to TRAIL-induced apoptosis compared to MDCK cells by all assessment methods. The dog genome assembly was searched for orthologs of TRAIL and its receptors using published sequences from other species for reference. Although a canine ortholog for TRAIL was identified, only one TRAIL receptor ortholog (TNFRSF11B) could be found. C2, but not MDCK, cells expressed mRNA for TNFRSF11B, detected by RT-PCR. In other species, TNFRSF11B is a decoy receptor, as even though it has a death domain it is secreted due to its lack of a transmembrane domain. The effect of TRAIL on the C2 cell line suggests that this cytokine might be suitable for treatment of mast cell tumors in dogs.
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PMID:Susceptibility of the C2 canine mastocytoma cell line to the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). 1918 23


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