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)

We examined the mechanism of the inflammatory response induced by topical application of mustard oil (0.5-20.0%/20 microliters per ear) to the mouse ear compared to that of the response to capsaicin. The dose-dependent increases in plasma extravasation and ear thickness reached a maximum at approximately 30 min after mustard oil application. Topical pretreatment of ears with capsaicin (250 micrograms/ear) diminished mustard oil-induced plasma extravasation for up to day 7 but not at day 14 after treatment. However, desensitization of the exudative response was not evoked by reapplication of mustard oil to ears. The inflammatory response to mustard oil did not differ between the ears of mast cell-deficient mice and those of the congenic normal mice. Mustard oil-induced plasma extravasation was unaffected by pretreatment with histamine H1 and 5-HT2 receptor antagonists and the capsaicin-functional inhibitor, ruthenium red, which inhibit capsaicin-induced ear oedema. The endopeptidase inhibitor, phosphoramidon, enhanced the ability of mustard oil to increase dye leakage. The tachykinin NK1 receptor antagonist, SR 140333 ((S)1-[2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pi peridin-3-yl]ethyl]-4-phenyl-1-azoniabicyclo[2.2.2.]octane, chloride), not only inhibited mustard oil-induced plasma extravasation but also blocked the enhancement by phosphoramidon of the response to mustard oil. In contrast, the tachykinin NK2 receptor antagonist, SR 48968 ((S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4,- dichlorophenyl)butyl]benzamide), and the tachykinin NK3 receptor antagonist, SR 142801 ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)pro pyl)-4- phenylpiperidin-4-yl)-N-methylacetamide), had no effect on plasma extravasation. The present results demonstrated that mustard oil induces mouse skin inflammation through a mechanism different from that for capsaicin. Mediators such as histamine and 5-HT from mast cells appear to be minor factors in the response to mustard oil. In addition, evidence supports the assumption that the tachykinin NK1 receptor is involved in this model.
 ...
PMID:Mechanism of mustard oil-induced skin inflammation in mice. 931 40

An increasing number of persons say that they get cutaneous problems as well as symptoms from certain internal organs, such as the central nervous system (CNS) and the heart, when being close to electric equipment. A major group of these patients are the users of video display terminals (VDTs), who claim to have subjective and objective skin- and mucosa-related symptoms, such as pain, itch, heat sensation, erythema, papules, and pustules. The CNS symptoms are, e.g. dizziness, tiredness, and headache. Erythema, itch, heat sensation, edema and pain are also common symptoms of sunburn (UV dermatitis). Alterations have been observed in cell populations of the skin of patients suffering from so-called "screen dermatitis" similar to those observed in the skin damaged due to ultraviolet (UV) light or ionizing radiation. In "screen dermatitis" patients a much higher number of mast cells have been observed. It is known that UVB irradiation induces mast cell degranulation and release of TNF-alpha. The high number of mast cells present in the "screen dermatitis" patients and the possible release of specific substances, such as histamine, may explain their clinical symptoms of itch, pain, edema and erythema. The most remarkable change among cutaneous cells, after exposure with the above-mentioned irradiation sources, is the disappearance of the Langerhans' cells. This change has also been observed in "screen dermatitis" patients, again pointing to a common cellular and molecular basis. The results of this literature study demonstrate that highly similar changes exist in the skin of "screen dermatitis" patients, as regards the clinical manifestations as well as alterations in the cell populations, and in skin damaged by UV light or ionizing radiation.
 ...
PMID:Skin changes in "screen dermatitis" versus classical UV- and ionizing irradiation-related damage--similarities and differences. 941 15

The present study was undertaken to characterize further the structure and function of cutaneous nerves which we have previously shown to associate with skin immune cells (Hosoi et al., Nature 1993: 363:159). Ultrastructurally, axons were prominent within the superficial dermis and epidermis in neonatal murine skin, but they were inconspicuous in adult murine and primate skin. Immunohistochemical and immunoultrastuctural evaluation of normal adult human and simian skin for neural cell adhesion molecule (N-CAM), however, defined a plexus of axons surrounding superficial dermal mast cells and extending as delicate, vertical branches into the overlying epidermal layer. Antibodies to neuropeptides substance P, calcitonin gene-related peptide, and to nerve cell-specific clathrin (LCb subunit) also reacted with this neural plexus. Double labeling disclosed intimate associations of N-CAM-positive axons with dermal chymase-positive mast cells as well as with epidermal CD1a-positive Langerhans' cells by confocal scanning laser microscopy. Functionally, capsaicin applied to forearm skin revealed by 6 h discharge of mast cell chymase and induction of E-selectin in adjacent microvascular endothelium, events consistent with release of substance P from axons and subsequent stimulation of cytokine-mediated mast cell-endothelial interaction. Identical application of capsaicin to human skin xenografted to immunodeficient mice, and thus experimentally lacking in unmyelinated axons, failed to show similar findings. These results provide additional support to the concept that an elaborate network of cutaneous axons may play a functional role in regulation of skin inflammation and immunity.
 ...
PMID:Characterization of unmyelinated axons uniting epidermal and dermal immune cells in primate and murine skin. 950 40

P-selectin, a member of the selectin family of adhesion molecules, mediates the initial adhesion of leukocytes to the blood vessel wall during their emigration from the circulation. Adhesion molecules play an important role in the pathogenesis of several diseases, including various skin conditions. The objectives of the present study were to characterize the expression of vascular P-selectin in the skin of dogs suffering from inflammatory diseases or from common cutaneous neoplasms, and to determine if a correlation exists between P-selectin expression and inflammatory cell infiltration in these conditions. Immunohistochemistry was performed on formalin-fixed canine skin using a specific anti-canine P-selectin monoclonal antibody (MD3). Results showed that P-selectin was minimally expressed in normal canine skin. However, the number of P-selectin-expressing blood vessels was significantly increased (P < 0.05) in cases of allergic dermatitis, autoimmune dermatitis, pyogranulomatous dermatitis, dermatophytosis, and panniculitis. Highest P-selectin expression (percentage of MD3-positive vessels and intensity of the reaction) was observed in cases of autoimmune and pyogranulomatous dermatitis (55.3+/-7.4 and 44.0+/-9.9% P-selectin-positive vessels, respectively). In all conditions studied, a positive correlation existed between the number of P-selectin-positive blood vessels and the number of infiltrating leukocytes (r=0.556, P < 0.01). A significant number of blood vessels in mast cell tumors also expressed P-selectin, whereas no staining was observed in any of the histiocytomas examined. These results reveal that P-selectin expression is increased in different types of canine inflammatory skin diseases and suggest that P-selectin could participate in the local recruitment of leukocytes in canine cutaneous diseases.
 ...
PMID:P-selectin expression in canine cutaneous inflammatory diseases and mast cell tumors. 953 61

The mast cell, which is a histamine-containing cell, has been found to have far more functions in skin inflammation than hitherto understood. To investigate the appearance of mast cells in prurigo nodularis, histamine immunohistochemistry in combination with nerve growth factor receptor (NGFr) double-staining as well as electron microscopic studies were performed. The results revealed that the histamine-containing cell number was increased in the lesional dermis. The mast cell size was also increased and the shape had become more dendritic. They tended to contact the epidermis and even infiltrated into it. In the histamine and NGFr double-staining, both an increased histamine-containing mast cell number and an increased number of NGFr-immunoreactive nerve fiber profiles were revealed in the upper dermis of the prurigo nodularis lesional skin. Mast cells were seen in close vicinity to NGFr-positive nerves and sometimes even seemingly to contact single nerve fibers. At the ultrastructural level, it is obvious that the mast cell bodies become larger, having more abundant cytoplasm and organelles (e.g. mitochondria), but comparatively fewer characteristic granules. Mast cells were often observed to sprout long dendrites, with or without granules. The cells were also frequently seen to contact other cell types, and a mast cell infiltration into the epidermis was also found. The statistical results of mast cell numbers showed a significant increase in prurigo nodularis lesional skin compared to the normal controls. The present results further indicate that mast cells, together with cutaneous nerve fibers, are actively involved in the pathogenesis of the disease.
 ...
PMID:Histamine-containing mast cells and their relationship to NGFr-immunoreactive nerves in prurigo nodularis: a reappraisal. 960 37

Vascular endothelial growth factor (VEGF) has been implicated in the pathologic angiogenesis observed in psoriasis and other chronic inflammatory skin diseases that are characterized by enhanced expression of VEGF by epidermal keratinocytes and of VEGF receptors by tortuous microvessels in the upper dermis. To investigate the functional importance of chronic VEGF overexpression in vivo, we used a keratin 14 promoter expression cassette containing the gene for murine VEGF164 to selectively target VEGF expression to basal epidermal keratinocytes in transgenic mice. These mice demonstrated an increased density of tortuous cutaneous blood capillaries with elevated expression levels of the high affinity VEGF receptors, VEGFR-1 and VEGFR-2, most prominently during the neonatal period. In contrast, no abnormalities of lymphatic vessels were detected. In addition, the number of mast cells in the upper dermis was significantly increased in transgenic skin. Intravital fluorescence microscopy revealed highly increased leukocyte rolling and adhesion in postcapillary skin venules that were both inhibited after injection of blocking antibodies against E- and P-selectin. Combined blocking antibodies against intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 were without effect, whereas an anti-vascular cell adhesion molecule-1/VLA-4 antibody combination almost completely normalized the enhanced leukocyte adhesion in transgenic mice. This study reveals VEGF as a growth factor specific for blood vessels, but not lymphatic vessels, and demonstrates that chronic orthotopic overexpression of VEGF in the epidermis is sufficient to induce cardinal features of chronic skin inflammation, providing a molecular link between angiogenesis, mast cell accumulation, and leukocyte recruitment to sites of inflammation.
 ...
PMID:Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. 966 79

The release of cytokines from cutaneous cells may be of major importance in the initiation and development of many inflammatory skin disorders. For example, tumor necrosis factor-alpha (TNF-alpha), which in healthy skin is found preformed only in mast cells, is able to induce the expression of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1). Increased expression of ICAM-1 occurs in keratinocytes in lesional skin of psoriasis and atopic dermatitis (AD) and it is considered to be an important initiator of leucocyte/keratinocyte interactions in skin inflammation. We counted the mast cells showing TNF-alpha immunoreactivity using a double-staining method in nonlesional and lesional skin sections from 12 patients with AD and 12 patients with psoriasis. The percentage of TNF-alpha+ mast cells in lesional and nonlesional AD skin was 36 +/- 22% and 21 +/- 15% (P < 0.018, paired t-test), respectively, and in psoriatic skin was 16 +/- 25% and 15 +/- 15%, respectively (P < 0.89, paired t-test). We also cultured whole skin biopsies taken from the healthy-looking skin of psoriatic and AD patients in the presence of mast cell degranulator compound 48/80, which resulted in focal expression of ICAM-1 in the epidermis. In cultured keratinocytes, both histamine and an extract of a human mast-cell line (HMC-1) induced ICAM-1 immunostaining only in occasional cells, but the combination of histamine and the HMC-1 extract resulted in intense ICAM-1 staining in numerous cells. This enhancement of ICAM-1 staining was abolished by preincubation of the HMC-1 extract with anti-TNF-alpha antibody. These results suggest that the degranulation of mast cells induces the expression of ICAM-1 in keratinocytes probably via TNF-alpha and histamine.
 ...
PMID:Mast cells of psoriatic and atopic dermatitis skin are positive for TNF-alpha and their degranulation is associated with expression of ICAM-1 in the epidermis. 974 89

Mast cells play an important role in the pathological development of many inflammatory and allergic diseases and inhibition of mast cell activation is a potential target for therapeutic intervention. Therefore, the effect of the novel ascomycin macrolactam derivative SDZ ASM 981 on Fc epsilonRI-mediated activation of rat basophilic leukemia (RBL) cells, as a model for mast cell activation, was investigated. First, the ability to inhibit different mast cell immunophilins in vitro was tested. Using recombinant macrophilin-12 (FKBP-12), inhibition of rotamase activity with an IC50 of approximately 6 nM was observed. The rotamase activity of cyclophilin A (18 kDa) was not affected. Secondly, the effect of SDZ ASM 981 on Fc epsilonRI-mediated mast cell activation was investigated in the RBL cell model. SDZ ASM 981 inhibited exocytosis of preformed mediators (e.g. serotonin) with an IC50 of approximately 30 nM. Transcription and release of newly synthesized mediators (e.g. TNF-alpha) was inhibited with an IC50 of approximately 100 nM. The inhibitory effect of SDZ ASM 981 was antagonized by rapamycin. We conclude that SDZ ASM 981 is a potent inhibitor of Fc epsilonRI-mediated activation of mast cells in vitro. The mechanism of action involves formation of (calcineurin) inhibitory complexes with macrophilins. We suggest that this inhibitory action on mast cells might contribute to the antiinflammatory effect of SDZ ASM 981 observed in vivo (e.g. in aptopic dermatitis and psoriasis).
 ...
PMID:Ascomycin macrolactam derivative SDZ ASM 981 inhibits the release of granule-associated mediators and of newly synthesized cytokines in RBL 2H3 mast cells in an immunophilin-dependent manner. 980 44

We examined the mechanisms of quinolone phototoxicity in vivo and in vitro. Simultaneous p.o. administration of a quinolone and ultraviolet-A (UVA) irradiation for 4 h induced auricular skin inflammation in BALB/c mice, including edema and neutrophil infiltration in the dermis. Antioxidants inhibited the inflammation in the early stage and cyclooxygenase inhibitors did in both the early and later stages, whereas 5-lipoxygenase inhibitors or histamine antagonists had no effect. The phototoxic inflammation was also induced in mast cell-deficient WBB6F1-W/Wv mice. Corresponding to the in vivo results, incubation with a quinolone under UVA irradiation stimulated BALB/c 3T3 mouse fibroblast cells to release prostaglandin E2 (PGE2) and 6-keto-PGF1alpha, but not leukotriene B4. In contrast, UVA-pre-irradiated quinolones did not affect PG release from fibroblasts. The PGE2 release was inhibited by cyclooxygenase inhibitors, antioxidants, protein kinase C (PKC) inhibitors and a tyrosine kinase (TK) inhibitor, but not by antibodies against tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1). These results lead to a hypothesis that reactive oxygen species generated from quinolones under UVA irradiation trigger PG release from dermal fibroblasts via PKC and TK activation, resulting in skin inflammation and that 5-lipoxygenase products, histamine, TNF alpha or IL-1 is ruled out from the mechanism.
 ...
PMID:Mechanisms of quinolone phototoxicity. 1002 81

Atopic dermatitis (AD) is thought to be induced by a complex of various allergic reactions and T cells are implicated in its etiology. Since tacrolimus strongly inhibits T cell activation, tacrolimus ointment has been developed as a novel drug for AD throughout the world. Tacrolimus inhibits mast cell and eosinophil activation and antigen presenting activity of Langerhans cells in vitro. In the in vivo experimental animal models of AD, such as contact and spontaneous dermatitis in mice and repeated hapten treated skin inflammation in rats, tacrolimus ointment showed inhibitory activity. In clinical studies with AD patients in Japan, USA and Europe, tacrolimus ointment showed a marked effect. In comparative studies in Japan, it showed the same efficacy as a strong class steroid ointment on eczema at the trunk and extremities and superior efficacy at the face and neck compared to a medium class steroid. The most prominent adverse event is experienced at the local application site with reactions such as a burning sensation and erythema. Systemic side effects were rarely observed. While there is a possibility of skin infections when using tacrolimus, skin atrophy, even after long term treatment, was not observed. Thus tacrolimus ointment could be an efficient alternative to steroid ointment for AD.
 ...
PMID:[Pharmacological profile and clinical effect of tacrolimus ointment (Protopic ointment) for atopic dermatitis]. 1141 45


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