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)

Mature human mast cells are tissue-residing, key effector cells of immediate allergic reactions. Moreover, mast cells have been recognized as a potent cellular source of multiple cytokines, suggesting an important role in immunoregulation and host defense. Here, we report on the regulation of mature human mast cells isolated from intestinal tissues by stem cell factor (SCF) and interleukin (IL)-4. SCF is substantially necessary for mast cell survival and induces marginal mast cell proliferation in vitro, whereas IL-4 by itself has no effects on mast cell survival or proliferation. Most interestingly, in synergy with SCF, IL-4 strongly enhances mast cell proliferation. In the presence of SCF, mast cells predominantly produce pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6, IL-8, IL-16, and IL-18. Addition of IL-4 to the culture medium induces the expression of Th2-type cytokines (IL-3, IL-5 and IL-13), and a downregulation of pro-inflammatory cytokines, namely IL-6. Furthermore, SCF by itself supports the predominance of the tryptase/chymase double-positive mast cell subtype MCTC whereas the addition of IL-4 supports the chymase negative MCT subtype. In conclusion, SCF may primarily regulate resident mast cell survival, whereas IL-4 may promote local proliferation of mast cells and their expression of Th2-type cytokines.
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PMID:Regulation of human intestinal mast cells by stem cell factor and IL-4. 1129 28

The crude drug "Siberian Ginseng (SG)" has long been used in empirical Oriental medicine for the nonspecific enhancement of resistance in humans and animals. In this study, we investigated the effect of cell cultured SG by oral administration in mast cell-mediated allergic reactions. SG dose-dependently inhibited compound 48/80-induced systemic allergy with doses of 10(-2) to 1 g/kg 1 h before oral administration. Of special note, SG inhibited systemic allergy with the dose of 1 g/kg by 25%. SG (1 g/kg) also inhibited passive cutaneous allergic reaction by 51%. SG dose-dependently inhibited histamine release from rat peritoneal mast cells. When SG (0.01 mg/ml) was added, the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 in antidinitrophenyl (DNP) IgE antibody-stimulated mast cells was inhibited 39.5% and 23.3%, respectively. In addition, SG inhibited anti-DNP IgE antibody-stimulated TNF-alpha protein expression in mast cells. Our studies provide evidence that SG may be beneficial in the treatment of various types of allergic diseases.
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PMID:Inhibitory effects of mast cell-mediated allergic reactions by cell cultured Siberian Ginseng. 1132 43

Stem cell factor (SCF) is directly involved in the induction of airway hyperreactivity during allergen-induced pulmonary responses in mouse models. In these studies, we examined the specific mediators and mechanisms by which SCF can directly induce airway hyperreactivity via mast cell activation. Initial in vitro studies with bone marrow-derived mast cells indicated that SCF was able to induce the production of bronchospastic leukotrienes, LTC(4) and LTE(4). Subsequently, when SCF was instilled in the airways of naive mice, we were able to observe a similar induction of LTC(4) and LTE(4) in the bronchoalveolar lavage (BAL) fluid and lungs of treated mice. These in vivo studies clearly suggested that the previously observed SCF-induced airway hyperreactivity may be related to the leukotriene production after SCF stimulation. To further investigate whether the released leukotrienes were the mediators of the SCF-induced airway hyperreactivity, an inhibitor of 5-lipoxygenase (5-LO) binding to the 5-LO activating protein (FLAP) was utilized. The FLAP inhibitor MK-886, given to the animals before intratracheal SCF administration, significantly inhibited the release of LTC(4) and LTE(4) into the BAL fluid. More importantly, use of the FLAP inhibitor nearly abrogated the SCF-induced airway hyperreactivity. In addition, blocking the LTD(4)/E(4), but not LTB(4), receptor attenuated the SCF-induced airway hyperreactivity. In addition, the FLAP inhibitor reduced other mast-derived mediators, including histamine and tumor necrosis factor. Altogether, these studies indicate that SCF-induced airway hyperreactivity is dependent upon leukotriene-mediated pathways.
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PMID:SCF-induced airway hyperreactivity is dependent on leukotriene production. 1135 Aug 4

Mast cells play a pivotal role in innate host immune response to gram-negative bacteria. We report that Janus kinase 3 plays a role in mast cell-mediated bacterial clearance and neutrophil recruitment by regulating the release of tumor necrosis factor from mast cells. The role of JAK3 in mast cell-facilitated neutrophil recruitment and bacterial clearance was investigated by comparing the neutrophil influxes and bacterial clearance in mast cell-deficient W/W(v) mice reconstituted with JAK3(+/+) or JAK(-/-) mast cells. The neutrophil influx, bacterial clearance, and survival outcome in W/W(v) mice reconstituted with JAK3(+/+) mast cells was better than in W/W(v) mice reconstituted with JAK3(-/-) mast cells. These findings provide evidence that JAK3 is a key regulator of mast cell-mediated innate immunity against gram-negative bacteria.
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PMID:Role of Janus kinase 3 in mast cell-mediated innate immunity against gram-negative bacteria. 1152 Apr 65

A case of ovarian fibrosarcoma producing multiple cytokines is presented. The tumor occurred in the left ovary of a Japanese woman with epigastralgia, remittent fever, leukocytosis and slight thrombocytosis with moderate increase of mast cells in bone marrow, but lack of hormonal abnormality. The resected tumor of the ovary was well encapsulated and it was composed of spindle-shaped tumor cells and scattered tubules with marked mast cell infiltration. The tumor recurred in the pelvic cavity 14 months later, accompanied by similar signs and symptoms as occurred with the primary tumor. Serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha were elevated. The recurrent tumor showed similar histological findings to those of the primary tumor, except for lack of tubules. Tumor cells revealed a focally positive immunoreaction for vimentin, IL-6 and TNF-alpha and alpha-inhibin. Reverse transcription-polymerase chain reaction using total RNA obtained from the recurrent tumor demonstrated mRNA expression of IL-6, IL-10, TNF-alpha and stem cell factor. This is a rare case of ovarian fibrosarcoma producing multiple cytokines, resulting in atypical clinical findings.
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PMID:Ovarian fibrosarcoma producing multiple cytokines. 1169 80

The herbal formulation ALLERGINA has been used against allergic inflammation disease for generations, and still occupies an important place in traditional medicine in Korea. In this study, we investigated the effect of ALLERGINA by oral administration in mast cell-mediated anaphylaxis responses. ALLERGINA dose-dependently inhibited compound 48/48-induced systemic anaphylaxis with doses of 10(-2) to 5 g/kg 1 h before orally administered. Of special note, ALLERGINA inhibited systemic anaphylaxis completely with doses of 1 g/kg and 5 g/kg. ALLERGINA (1 g/kg) also inhibited passive cutaneous anaphylaxis by 84%. ALLERGINA dose-dependently inhibited histamine release from rat peritoneal mast cells. When ALLERGINA (0.01 mg/ ml) was added, ALLERGINA inhibited the production of tumor necrosis factor-alpha and interleukin-6, 80% and 26%, respectively in anti-dinitrophenyl IgE antibody-stimulated mast cells. Our studies provide evidence that ALLERGINA may be beneficial in the treatment of allergic inflammation diseases.
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PMID:Effect of allergina on mast cell-mediated allergic reactions. 1179 21

We studied the effect of Acanthopanax senticosus stem (ACPS) on mast cell-dependent anaphylaxis. ACPS inhibited compound 48/80-induced systemic anaphylaxis at a dose of 1.0 g/kg by 50%. ACPS also inhibited passive cutaneous anaphylaxis reaction and histamine release from mast cells in a dose-dependent manner, respectively. Moreover, ACPS had an inhibitory effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha (TNF-alpha) production from mast cells. These results indicate that ACPS inhibits mast cell-mediated anaphylaxis in vivo and in vitro murine model.
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PMID:Effect of Acanthopanax senticosus stem on mast cell-dependent anaphylaxis. 1184 40

Variations in the host response during pneumonia caused by Streptococcus pneumoniae in susceptible (CBA/Ca) and resistant (BALB/c) inbred mouse strains were investigated. Significant differences were detected in survival time, core body temperature, lung-associated and systemic bacterial loads, mast cell numbers, magnitude and location of cytokine production, lung disruption, and ability of isolated lung cells to release the cytokine tumor necrosis factor (TNF) alpha in vitro. Overall, the results indicate that the reduced capacity of CBA/Ca mice to induce rapid TNF activity within the airways following infection with S. pneumoniae may be a factor in their elevated susceptibility to pneumococcal pneumonia.
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PMID:Role of inflammatory mediators in resistance and susceptibility to pneumococcal infection. 1185 43

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

Human mast cells are multifunctional tissue-dwelling cells that play a crucial role in eosinophil-dependent disorders, such as asthma and parasitic diseases, by the secretion of eosinophil-active mediators. Mast cell-derived cytokines, generated in response to cross-linking of the high-affinity IgE receptor, can regulate eosinophil activation, survival, and chemotaxis. In this study, mast cells generated from human cord blood progenitors (stem cells) were studied for eosinophil-active inflammatory cytokine expression. Cord blood-derived mast cells (CBDMC) expressed typical intracellular scroll granules and microvilli-like structures on their cell surfaces, demonstrated the presence of tryptase, and elaborated prostaglandin D2 (PGD2) after cross-linkage of the high-affinity receptor for IgE (FcepsilonRI). CBDMC expressed tumor necrosis factor-alpha (TNF-alpha) and the eosinophil-active growth factors, interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after activation. (IL-1beta greatly enhanced IgE-dependent production of these cytokines in response to FcepsilonRI cross-linkage, suggesting a role for bystander/phagocytic cells in modulating mast cell function. In contrast, interferon-alpha (IFN-alpha) inhibited IL-5 and GM-CSF generation, and the glucocorticoid, dexamethasone (Dex), inhibited production of IL-5 and GM-CSF from CBDMC. A macrophage-mast cell-eosinophil axis may exist in vivo that may be susceptible to pharmacologic manipulation.
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PMID:Regulation of eosinophil-active cytokine production from human cord blood-derived mast cells. 1203 46


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