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

To investigate the regulation of mouse L-histidine decarboxylase (HDC) gene expression, we isolated genomic DNA clones encoding HDC. Structural analysis revealed that the mouse HDC gene was composed of 12 exons, spanning approximately 24 kb. Northern blotting analysis indicated that, among the cell lines examined, a high level of HDC gene expression was restricted to mature mast cell lines and an erythroblastic cell line. The gene was induced strongly in the mouse immature mast cell line P815 after incubation in the peritoneal cavity of BDF1 mice. We observed that the promoter region was demethylated in the HDC-expressing cell lines and in induced P815 cells. Interestingly, forced demethylation by 5-azacytidine (5-azaC) treatment induced high expression of HDC mRNA in P815 cells. The activity of a mouse HDC promoter-reporter construct stably transfected in P815 cells was repressed by in vitro patch-methylation. This low promoter activity of the patch-methylated reporter construct was restored after 5-azaC treatment, which demethylated the patch-methylated promoter. These results indicate that DNA methylation state of the promoter region controls HDC gene expression.
 ...
PMID:The mouse L-histidine decarboxylase gene: structure and transcriptional regulation by CpG methylation in the promoter region. 1090 16

Both histamine and polyamines are important for maintaining basophilic cell function and viability. The synthesis of these biogenic amines is regulated by histidine decarboxylase and ornithine decarboxylase, respectively. In other mammalian tissues, an interplay between histamine and polyamine metabolisms has been suspected. In this report, the interplay between histamine and ornithine-derived polyamines was studied in a non-transformed mouse mast cell line (C57.1) treated with phorbol ester and dexamethasone, a treatment previously used to increase histidine decarboxylase expression in mastocytoma and basophilic leukemia. Treatment with phorbol ester and dexamethasone increased histidine decarboxylase expression and intracellular histamine levels in C57.1 mast cells to a greater extent than those found for other transformed basophilic models. The treatment also induced a reduction in ornithine decarboxylase expression, intracellular polyamine contents, and cell proliferation. These results indicate that the treatment induces a co-ordinate response of polyamine metabolism and proliferation in mast cells and other immune-related cells. The decrease in the proliferative capacity of mast cells caused by phorbol ester and dexamethasone was simultaneous to an increase in histamine production. Our results, together with those reported by other groups working with polyamine-treated mast cells, indicate an antagonism between histamine and polyamines in basophilic cells.
 ...
PMID:Effects of phorbol ester and dexamethasone treatment on histidine decarboxylase and ornithine decarboxylase in basophilic cells. 1130 Oct 43

Stimulation of RAW 264.7 cells with the Ca(2+)-ATPase inhibitor thapsigargin increased histamine production. Immunoblot analyses revealed that thapsigargin increased the expression of 74-kDa histidine decarboxylase protein although rat mast cell line RBL-2H3 cells express both 74- and 53-kDa histidine decarboxylase proteins. The inhibition of histamine production by the mitogen-activated protein kinase-extracellular signal-regulated kinase kinase (MEK) inhibitors PD98059 (2'-amino-3'-methoxyflavone) and U0126 (1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene) and by the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole) was correlated with the inhibition of the expression of thapsigargin-induced 74-kDa histidine decarboxylase protein. The synthetic glucocorticoid dexamethasone inhibited thapsigargin-induced histamine production and 74-kDa histidine decarboxylase protein expression. The thapsigargin-induced activation of p42/p44 MAP kinase and p38 MAP kinase was also inhibited by dexamethasone. These findings indicate that the induction of histamine production by thapsigargin in RAW 264.7 cells is due to the increased expression of 74-kDa histidine decarboxylase protein and that dexamethasone inhibits thapsigargin-induced histidine decarboxylase protein expression and histamine production via inhibition of MAP kinase activation.
 ...
PMID:Expression of 74-kDa histidine decarboxylase protein in a macrophage-like cell line RAW 264.7 and inhibition by dexamethasone. 1133 61

A biscoclaurin alkaloid preparation, cepharanthin (Ceph), is reported to have opposing pharmacological effects, enhancement or depression, on several cells and tissues, although detailed mechanisms remain unclear. Previously, we reported that Ceph enhanced lipopolysaccharide (LPS)-induced histidine decarboxylase (HDC) activity in mice spleens by consecutive pre-administration. In this study, we examined the pharmacological effects on HDC activity of a single Ceph pre-administration to test the influence of the administration method. Consequently, HDC activities were decreased by a single administration 15 minutes before LPS challenge in ddY and ICR mice spleens. Moreover, to further examine this suppressing effect, we employed genetically mast cell-deficient WBB6F1 W/Wv (W/Wv) mice to avoid the influence of mast cells. In W/Wv mice, HDC activity was enhanced, but not in the congenic WBB6F1 +/+ mice. These findings suggest that mast cells influence the depressant effect on HDC activity by a Ceph single administration in mast cell sufficient mice.
 ...
PMID:Opposing pharmacological actions of cepharanthin on lipopolysaccharide-induced histidine decarboxylase activity in mice spleens. 1138 91

Regulation of leukocyte migration and activation by chemokines are recognized as potentially important functions in the induction of acute and chronic inflammatory reactions. Regulated upon activation normal T cell expressed and presumably secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), and related molecules constitute the C-C class of the beta chemokine supergene family with inflammatory properties. Here we report that in experimental studies RANTES and MCP-1 provoke mast cell activation and increase histidine decarboxylase mRNA expression in a dose-dependent manner. Moreover, injections of RANTES and MCP-1 in the rat skin cause mast cell, eosinophil, and macrophage recruitment, and prostaglandin E2 (PGE2) generation. In a chronic inflammatory model MCP-1 was found to mediate the recruitment of mononuclear cells in calcified granulomas. In addition, MCP-1 mediated parasitic infections caused by Trichinella spiralis. In accordance with other studies, RANTES and MCP-1 were found to play an important role in the lung allergic inflammation, lung leukocyte infiltration, bronchial hyperresponsiveness, and the recruitment of eosinophils in the pathogenesis of asthma. Here for the first time we propose a new mechanism of pulmonary airway inflammation where RANTES and MCP-1 are deeply involved. We also studied the apparent role played by RANTES in the pathogenesis of relapsing-remitting multiple sclerosis enhancing the inflammatory response within the nervous system.
 ...
PMID:MCP-1 and RANTES are mediators of acute and chronic inflammation. 1142 73

Histidine decarboxylase (HDC) synthesizes histamine from histidine in mammals. To evaluate the role of histamine, we generated HDC-deficient mice using a gene targeting method. The mice showed a histamine deficiency and lacked histamine-synthesizing activity from histidine. These HDC-deficient mice are viable and fertile but exhibit a decrease in the numbers of mast cells while the remaining mast cells show an altered morphology and reduced granular content. The amounts of mast cell granular proteases were tremendously reduced. The HDC-deficient mice provide a unique and promising model for studying the role of histamine in a broad range of normal and disease processes.
 ...
PMID:Mice lacking histidine decarboxylase exhibit abnormal mast cells. 1147 47

Mast cells are differentiated in vitro from bone marrow precursors. In this study the development of bone marrow-derived mast cells was examined from histidine decarboxylase deficient (HDC-/-) and wild-type mice in the presence of IL-3. The number of non-adherent, tryptase- and c-kit-positive mast cells in bone marrow-derived cultures of HDC(-/-) mice was decreased compared to that of wild-type (HDC+/+) animals, but within the tryptase- and c-kit-positive cells there was no difference in the expression intensity of both markers between the two groups. Furthermore, less serine proteases mMCP5, mMCP6 and FcepsilonRIalpha mRNA were detected in bone marrow-derived cell cultures originating from HDC-/- mice. Antigen-provoked degranulation through high-affinity FcepsilonI receptor was also lower in HDC-/- mice. The colony assays in semisolid medium yielded a significantly lower ratio of mixed colonies and higher proportion of macrophage colonies from HDC-/- mice-derived bone marrow compared to the wild-type. In the course of the differentiation of HDC-/- --derived mast cells exogenously added histamine is unable to substitute the endogenously missing histamine. Concordantly, alpha-fluoromethyl-histamine, the specific inhibitor of HDC, revealed only a marginal inhibition on the differentiation of tryptase-positive mast cells from wild-type mice. These findings suggest that the effect of histamine on the IL-3-dependent development of bone marrow-derived mast cell differentiation during the early period is crucial and irreplaceable.
 ...
PMID:Bone marrow-derived mast cell differentiation is strongly reduced in histidine decarboxylase knockout, histamine-free mice. 1193 74

We have analyzed the role of histamine in the angiogenesis of the granulation tissue in histidine decarboxylase-deficient (HDC(-/-)) mice, mast cell-deficient mice (WBB6F1-W/W(V)), and their corresponding wild-type mice (HDC(+/+) and WBB6F(1)(+/+)). In HDC(+/+) mice, subcutaneous implantation of a cotton thread in the dorsum induced granulation tissue formation with angiogenesis, while the topical injection of anti-vascular endothelial growth factor (VEGF) IgG strongly suppressed them. In HDC(-/-) mice which showed lower VEGF levels in the granulation tissue, there was notably less angiogenesis and granulation tissue formation than in HDC(+/+) mice. The topical injection of histamine or the H(2) agonist dimaprit rescued the defective angiogenesis and granulation tissue formation in HDC(-/-) mice. There was no significant difference in the granulation tissue formation and angiogenesis between WBB6F1-W/W(V) and WBB6F1(+/+) mice. In addition, macrophages in the granulation tissue were found to express HDC. Our findings indicate that histamine derived from non-mast cells plays a significant role in the angiogenesis of the inflammatory granulation tissue.
 ...
PMID:Defective angiogenesis in the inflammatory granulation tissue in histidine decarboxylase-deficient mice but not in mast cell-deficient mice. 1195 88

Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. To evaluate the role of histamine in skin allergic reaction, we used HDC gene knockout mice lacking histamine. No plasma extravasation reaction was observed in HDC-/- mice after passive cutaneous anaphylaxis (PCA) test. Compound 48/80, a mast cell granule depletor, produced plasma extravasation inHDC+/+ mice but no extravasation in HDC-/- mice. Interestingly, orally administered histamine was distributed in the skin in HDC-/- mice and in these histamine-supplemented mice the plasma extravasation reaction was observed after the injection of compound 48/80 and the PCA test. Cultured bone marrow-derived mast cells of HDC-/- mice took up histamine from the histamine-supplemented medium into the secretory granules. The absorbed histamine was released in response to the same antigen and antibody combination used as in PCA test. In contrast to the immediate-type response, the delayed-type hypersensitive response, observed as a thickening of the ear skin after trinitrochlorobenzene challenge (following sensitization), showed no differences between HDC+/+ and HDC-/- mice. Therefore, among the allergic skin reactions, histamine is revealed to be an important mediator especially for the plasma extravasation in an immediate-type allergy model.
 ...
PMID:Plasma extravasation induced by dietary supplemented histamine in histamine-free mice. 1211 53

Because the Falck-Hillarp formaldehyde fluorescence method, which was superbly applied to identify catecholaminergic and serotonergic neurons, is not applicable to histamine, the first author (T.W.) developed an antibody to L-histidine decarboxylase (HDC) for identification of the histaminergic neuron system in the brain. The anti-HDC antibody was of great use for mapping the location and distribution of this histaminergic neuron system. (S)-alpha-fluoromethylhistidine, a specific and potent irreversible inhibitor of HDC, was also very useful in studies on functions of the neuron system. The activity of HDC is increased by various agents, treatments, and physiological conditions. We found new compounds that increased HDC activity (i.e., tetradecanoylphobol acetate (TPA), other tumor promoters, and staphylococcal enterotoxin A); and using mast cell-deficient mutant (W/W(v)) mice, we obtained evidence that this increase occurred in macrophages. To further characterize the mechanism of increases in HDC activity, the second author (H.O.) cloned human HDC cDNA and a human HDC gene. In studies on the regulation mechanism of the HDC gene, which is expressed only in limited types of cells such as mast cells, enterochromaffin-like cells in the stomach, cells in the tuberomammillary nucleus of the brain, and macrophages, CpG islands in the promoter region of the HDC gene were found to be demethylated in cells expressing the gene, whereas they are methylated in other cells that do not express the HDC gene. In collaboration with many other researchers, we developed HDC knockout mice. The resulting research is producing a lot of interesting findings in our laboratory as well as in others. In summary, HDC has been and will be useful in studies on functions of histamine.
 ...
PMID:L-histidine decarboxylase as a probe in studies on histamine. 1246 48


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