Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mast cells are traditionally known for mediating allergic reactions. In addition, these cells have been implicated in the pathogenesis of a variety of clinical conditions such as atopic and contact dermatitis, bullous pemphigoid, fibrotic lung disease, neurofibromatosis, psoriasis, scleroderma, rheumatoid arthritis, interstitial cystitis, ulcerative colitis, and Crohn's disease, but their role in host defense was an enigma until recently. Owing to the strategic location of mast cells at the host environment interface, their role in bacterial infections has been studied by a number of investigators. Latest reports show that mast cells have an ability to modulate the host's innate immune response to infectious agents. This review discusses the clinical implications of mast cell-bacteria interactions.
J Mol Med (Berl) 1998 Aug
PMID:Clinical implications of mast cell-bacteria interaction. 972 64

Benzoyl peroxide is a free-radical generating compound widely used in the polymer industry and also in pharmaceuticals as antimicrobial agent to treat acne. However, benzoyl peroxide causes irritation and contact dermatitis in about 1% of patients. Concern over the use of this compound is motivated by the demonstration that it can also act as skin tumor promoter in mice. In addition, benzoyl peroxide induces DNA strand breaks in many cells, including keratinocytes. Benzoyl peroxide toxicity is presumably mediated by the formation of reactive free radicals and by the consumption of intracellular antioxidants. In this work we investigated the effect of both the lipophilic antioxidant alpha-tocopherol and the hydrophilic thiol donor N-acetylcysteine (NAC) in human keratinocyte line HaCaT exposed to benzoyl peroxide. A protective effect against benzoyl peroxide cytotoxicity was achieved when cells were grown on a alpha-tocopherol layer. On the contrary, the addition of alpha-tocopherol dissolved in ethanol had a pro-oxidant effect, leading to an enhancement of benzoyl peroxide toxicity. Cytotoxicity was also reduced adding NAC to the culture medium; the presence of both NAC and alpha-tocopherol exerts a synergistic cytoprotection.
J Biochem Mol Toxicol 2004
PMID:Effect of alpha-tocopherol and N-acetylcysteine on benzoyl peroxide toxicity in human keratinocytes. 1512 53

The binding of sphingoid bases to peroxisome proliferator-activated receptor (PPAR) has been detected in a solid-phase binding assay. However, sphingoid base-induced changes in PPAR transactivation activity have not been examined. In this report, we show by reporter gene analyses that phytosphingosine (PS), a natural sphingoid base, activates the transcriptional activity of PPARs in the immortalized human keratinocyte, HaCaT. Real-time PCR analyses showed that the mRNA level of PPARgamma was increased after PS treatment in HaCaT cells in a dose- and time-dependent manner. Because PPARs play important roles in skin barrier homeostasis by regulating epidermal cell growth, terminal differentiation, and inflammatory response, we examined the effect of PS on normal human epidermal keratinocytes (NHEKs) and mouse skin. PS increased the production of cornified envelope in NHEKs by approximately 1.8-fold compared with controls. Epidermal differentiation marker proteins such as involucrin, loricrin, and keratin1 were also increased in PS-treated NHEKs, by ELISA or Western blotting analysis. A [(3)H]thymidine incorporation assay showed that PS inhibited DNA synthesis in NHEKs to 20% compared with controls. The antiproliferative and anti-inflammatory effects of PS were examined in a mouse model of irritant contact dermatitis produced by topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA). PS blocked epidermal thickening and edema and the infiltration of inflammatory cells into the dermis in the skin of TPA-treated hairless mice. The anti-inflammatory effects of PS were confirmed by the observation that PS blocked the TPA-induced generation of prostaglandin E(2) in peripheral mononuclear leukocytes. Taken together, our results provide an insight into the multiple regulatory roles of PS in epidermal homeostasis, and furthermore point to the potential use of PS as a therapeutic agent in the treatment of inflammatory and proliferative cutaneous diseases.
Mol Med
PMID:Phytosphingosine stimulates the differentiation of human keratinocytes and inhibits TPA-induced inflammatory epidermal hyperplasia in hairless mouse skin. 1683 68

The assessment of the skin sensitising capacity of chemicals is up to now investigated using in vivo animal tests. However there has been an increasing public and governmental concern regarding the use of animals for chemical screening. This has raised the need for the development of validated in vitro alternatives. Langerhans cells are potent antigen-presenting cells that play a crucial role in the development of allergic contact dermatitis. We used CD34(+) progenitor-derived dendritic cells from cord blood as an in vitro alternative for Langerhans cells. The cells were exposed to four contact allergens (nickel sulphate, dinitrochlorobenzene, oxazolone and eugenol) and two irritants (sodium dodecyl sulphate and benzalkonium chloride) for 3, 6, 12 and 24h. Using microarray analyses we revealed a set of 25 genes with an altered gene expression pattern after exposure to allergens and not to irritants. Five out of these 25 genes were selected and their gene expression changes were confirmed with real-time reverse transcriptase polymerase chain reaction. The list of 25 genes represent valuable candidates to be further evaluated for their capacity to predict the sensitizing potential of different classes of chemicals in studies using a more extended set of (non) allergic substances.
Mol Immunol 2007 May
PMID:Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. 1737 97

Many amines are skin irritants and cause contact dermatitis. However, little is known about their mechanisms of action in keratinocytes except that they induce the release of the inflammatory mediators cytokines and ATP. Here, we tested whether volume-regulated anion channels (VRACs) in primary cultures of normal human epidermal keratinocytes are modulated by the referenced amine-containing cutaneous irritant heptylamine. Under isotonic conditions, we isolated the VRAC current (I(VRAC)) from other conductances using a high Ca(2+)-buffering internal solution. I(VRAC) ran up after patch rupturing and reached a plateau within 15 min. It was reversibly and dose-dependently inhibited by heptylamine with an IC(50) value of 260 microM. Cell-swelling caused by the application of a hypotonic solution increased 2.7-fold I(VRAC) and reduced the inhibition of VRAC by heptylamine with a dose-response curve shifted approximately 10-fold to the right. In addition, we showed, using cell-attached patch recordings, that adding heptylamine to the bath inhibited VRAC activity. This suggests that heptylamine diffuses into the membrane to inhibit VRAC. Finally, we demonstrated that heptylamine induced Ca(2+)-store depletion and that VRAC inhibition was not caused by the increase in cytosolic Ca(2+). Taken together, these results identify heptylamine as a blocker of VRAC and suggest that Ca(2+)-store depletion may be involved in mechanisms of irritant contact dermatitis caused by heptylamine.
Mol Pharmacol 2007 Jun
PMID:The amine-containing cutaneous irritant heptylamine inhibits the volume-regulated anion channel and mobilizes intracellular calcium in normal human epidermal keratinocytes. 1738 25

A common polymorphism in the chitotriosidase gene (CHIT1) exists in which a 24 bp duplication in exon 10 results in aberrant splicing and deletion of 87 nucleotides. In this study, the gene frequency was found to be 0.56 (n=2054) in subjects of Asian ancestry, 0.17 (n=984) in subjects of European ancestry and 0.07 (n=536) in subjects of African ancestry. Notably, the median enzyme activity in wild-type subjects (TT) was much higher in subjects of European ancestry (2.69 mU/ml, n=202 subjects), than subjects of African (2.57 mU/ml, n=230 subjects) (P<0.0001) and Asian ancestry (0.86 mU/ml, n=114 subjects) (P<0.0001). The question of why chitotriosidase deficiency exists at such a high frequency is a challenging one. We postulated that if there was a selective advantage for chitotriosidase deficiency then there would be polymorphisms that would be associated with reduced enzyme activity independent of the 24 bp duplication. We found that the G102S and the A442G polymorphisms found occurring in subjects of all ancestries were not significantly associated with a reduction of enzyme activity. In contrast, the G354R (P<0.0001) and the A442V (P=0.0013) polymorphisms occurring predominantly in subjects of African ancestry were significantly associated with reduced chitotriosidase activity. We also investigated the possibility that chitotriosidase deficiency was associated with tuberculosis or with atopy, including allergic rhinitis, contact dermatitis, food or drug allergies and asthma.
Blood Cells Mol Dis
PMID:Human chitotriosidase polymorphisms G354R and A442V associated with reduced enzyme activity. 1769 2

Garlic (Alllium sativum L., Fam Liliaceae) is used medicinally mainly for the treatment of hypercholesterolemia and prevention of arteriosclerosis. Clinical trials have consistently shown that "garlic breath" and body odor are the most common (and well-documented) complaints associated to garlic intake. Case reports have highlighted the possibility that garlic use may cause allergic reactions (allergic contact dermatitis, generalized urticaria, angiedema, pemphigus, anaphylaxis and photoallergy), alteration of platelet function and coagulation (with a possible risk of bleeding), and burns (when fresh garlic is applied on the skin, particularly under occlusive dressings). Consumption of garlic by nursing mothers modifies their infant's behavior during breast-feeding. Finally, garlic may enhance the pharmacological effect of anticoagulants (e. g. warfarin, fluindione) and reduce the efficacy of anti-AIDS drugs (i. e. saquinavir).
Mol Nutr Food Res 2007 Nov
PMID:Garlic (Allium sativum L.): adverse effects and drug interactions in humans. 1791 62

Contact hypersensitivity (CHS) is a common skin disease, presenting clinically as allergic contact dermatitis. At inflammatory sites in a typical CHS model in the mouse ear, elevated expression of monocyte chemoattractant protein-1 (MCP-1) has been reported. MCP-1 is a potent chemotactic factor for many types of leukocytes including monocytes/macrophages and T cells. In this study, we aimed at developing a therapy for CHS involving RNA interference targeting MCP-1. A short interfering RNA (siRNA) to mouse MCP-1 successfully inhibited the secretion of MCP-1 by a fibroblastic cell line, L929, and RAW 264.7 cells derived from macrophages, and strikingly suppressed ear swelling in a CHS model. The siRNA systemically administered inhibited the infiltration of both monocytes/macrophages and T cells in the CHS model. Atelocollagen was used in this therapy as a delivery reagent for siRNA into the animal body. Atelocollagen facilitated the incorporation of the siRNA into macrophages/monocytes and fibroblasts, which vigorously secrete MCP-1 protein at inflammatory sites in CHS. This therapy had no adverse effects such as induction of interferon, or liver or renal damage. Our data indicate that the systemic delivery of siRNA targeting MCP-1 is a potent therapeutic strategy for CHS treatment.
Mol Ther 2008 Feb
PMID:Downregulation of monocyte chemoattractant protein-1 involving short interfering RNA attenuates hapten-induced contact hypersensitivity. 1805 72

A hierarchical classification study was carried out based on a set of 70 chemicals-35 which produce allergic contact dermatitis (ACD) and 35 which do not. This approach was implemented using a regular ridge regression computer code, followed by conversion of regression output to binary data values. The hierarchical descriptor classes used in the modeling include topostructural (TS), topochemical (TC), and quantum chemical (QC), all of which are based solely on chemical structure. The concordance, sensitivity, and specificity are reported. The model based on the TC descriptors was found to be the best, while the TS model was extremely poor.
J Comput Aided Mol Des
PMID:Predicting allergic contact dermatitis: a hierarchical structure-activity relationship (SAR) approach to chemical classification using topological and quantum chemical descriptors. 1833 24

In Asian countries where the Buddhism and Taoism are mainstream religions, incense burning is a daily practice. A typical composition of stick incense consists of 21% (by weight) of herbal and wood powder, 35% of fragrance material, 11% of adhesive powder, and 33% of bamboo stick. Incense smoke (fumes) contains particulate matter (PM), gas products and many organic compounds. On average, incense burning produces particulates greater than 45 mg/g burned as compared to 10 mg/g burned for cigarettes. The gas products from burning incense include CO, CO2, NO2, SO2, and others. Incense burning also produces volatile organic compounds, such as benzene, toluene, and xylenes, as well as aldehydes and polycyclic aromatic hydrocarbons (PAHs). The air pollution in and around various temples has been documented to have harmful effects on health. When incense smoke pollutants are inhaled, they cause respiratory system dysfunction. Incense smoke is a risk factor for elevated cord blood IgE levels and has been indicated to cause allergic contact dermatitis. Incense smoke also has been associated with neoplasm and extracts of particulate matter from incense smoke are found to be mutagenic in the Ames Salmonella test with TA98 and activation. In order to prevent airway disease and other health problem, it is advisable that people should reduce the exposure time when they worship at the temple with heavy incense smokes, and ventilate their house when they burn incense at home.
Clin Mol Allergy 2008 Apr 25
PMID:Incense smoke: clinical, structural and molecular effects on airway disease. 1843 80


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