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)

Tissue eosinophilia prevention represents one of the primary targets to new anti-allergic therapies. As lipoxin A4 (LXA4) and aspirin-triggered 15-epi-LXA4 (ATL) are emerging as endogenous "stop signals" produced in distinct pathologies including some eosinophil-related pulmonary disorders, we evaluated the impact of in situ LXA4/ATL metabolically stable analogues on allergen-induced eosinophilic pleurisy in sensitized rats. LXA4/ATL analogues dramatically blocked allergic pleural eosinophil influx, while concurrently increasing circulating eosinophilia, inhibiting the earlier edema and neutrophilia associated with allergic reaction. The mechanisms underlying this LXA4/ATL-driven allergic eosinophilia blockade was independent of mast cell degranulation and involved LXA4/ATL inhibition of both IL-5 and eotaxin generation, as well as platelet activating factor action. These findings reveal LXA4/ATL as a novel class of endogenous anti-allergic mediators, capable of preventing local eosinophilia.
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PMID:Cutting edge: lipoxin (LX) A4 and aspirin-triggered 15-epi-LXA4 block allergen-induced eosinophil trafficking. 1067 58

Previous investigations have provided evidence that the N-terminal peptide of annexin 1 (peptide Ac2-26) has the capacity of reproducing the anti-inflammatory actions of the full-length protein in many systems. In the current study, we report the effectiveness of the peptide Ac2-26 as an antiallergic tool in a model of rat pleurisy and provide indication for some of the mechanisms involved. In rats inflamed by injection of ovalbumin into the pleural cavity 14 days postsensitization, peptide Ac2-26 (50-200 microg/cavity) inhibited mast cell degranulation, plasma protein leakage, and the accumulation of both neutrophils and eosinophils. Treatment with either peptide Ac2-26 (200 microg/cavity) or dexamethasone (1 mg/kg i.p.) inhibited ovalbumin-induced eotaxin release in the pleural effluents. In vitro, peptide Ac2-26 inhibited ovalbumin-evoked histamine release from subcutaneous tissue fragments obtained from sensitized rats (33-66 microM) and interleukin-13-evoked eotaxin generation from cultured rat mesothelial cells (16-33 microM) but not eosinophil chemotaxis. This work demonstrates that the annexin 1 mimetic peptide Ac2-26 prevents allergen-evoked eosinophilic inflammatory response in rats. Combined analysis of the in vivo and in vitro experiments presented herein suggests that the blockade of secretion of pivotal mediators for the allergic response, such as histamine and eotaxin, could be responsible for the inhibitory actions displayed by peptide Ac2-26.
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PMID:A novel effect for annexin 1-derived peptide ac2-26: reduction of allergic inflammation in the rat. 1578 54

A previous study showed that the novel tetrazolephtalimide derivative LASSBio 552 (2-4-[3-(1H-1,2,3,4-tetraazol-5-yl)propoxy]phenethyl-1,3-isoindolinedione) prevents LTD(4)-evoked tracheal contraction. This led us to examine the putative anti-inflammatory effect of LASSBio 552 in comparison with the leukotriene CysLT(1) receptor antagonist zafirlukast using a model of allergic pleurisy in rats. Treatment with either LASSBio 552 (24-96 micromol/kg, i.p.) or zafirlukast (9-72 micromol/kg, i.p.), 1 h before challenge, inhibited eosinophil and mononuclear cell influx into the pleural cavity 24 h post-challenge, but failed to alter the increased levels of eotaxin, plasma leakage, mast cell degranulation and neutrophil infiltration noted 6 h post-challenge. CD4(+) T cell recruitment 24 h post-challenge was also sensitive to LASSBio 552. This treatment failed to alter cysteinyl leukotriene production at 6 h, but clearly inhibited the phenomenon 24 h and 48 h post-challenge. In in vitro settings LASSBio 552 inhibited allergen-evoked cysteinyl leukotriene generation from isolated mast cells, while histamine release remained unchanged. It also slightly inhibited cysteinyl leukotriene production by eosinophils and mononuclear cells triggered by Ca(+2) ionophore A23187. A leukotriene CysLT(1) receptor transfected cell-based assay revealed that LASSBio 552 did not prevent LTD(4)-evoked Ca(+2) influx, indicating that it was not a leukotriene CysLT(1) receptor antagonist. These findings indicate that LASSBio 552 is able to inhibit eosinophil influx triggered by allergen chalenge in a mechanism at least partially associated with suppression of CD4(+) T cell influx and cysteinyl leukotriene production.
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PMID:Evaluating the prophylactic potential of the phtalimide derivative LASSBio 552 on allergen-evoked inflammation in rats. 1579 91

New therapeutic approaches for the treatment of allergic diseases can be aided by the development of agents capable of regulating eosinophilic leukocytes. Here, we evaluated the anti-allergic properties of a crude extract of the Brazilian bromeliaceae Nidularium procerum, focusing on its effects on allergic eosinophilia. By studying allergic pleurisy in actively sensitized C57Bl/6 mice, we observed that pretreatment with N. procerum (2 mg/kg; i.p.) reduced pleural eosinophil influx triggered by allergen challenge. N. procerum was also able to reduce lipid body numbers found within infiltrating eosinophils, indicating that N. procerum in vivo is able to affect both migration and activation of eosinophils. Consistently, pretreatment with N. procerum blocked pleural eosinophil influx triggered by PAF or eotaxin, key mediators of the development of allergic pleural eosinophilia. The effect of N. procerum was not restricted to eosinophils, since N. procerum also inhibited pleural neutrophil and mononuclear cell influx. Of note, N. procerum failed to alter the acute allergic reaction, characterized by mast cell degranulation, oedema, and cysteinyl leukotriene release. N. procerum also had direct effects on murine eosinophils, since it inhibited both PAF- and eotaxin-induced eosinophil chemotaxis on an in vitro chemotactic assay. Therefore, N. procerum may be a promising anti-allergic therapy, inasmuch as it presents potent anti-eosinophil activity.
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PMID:Anti-allergic properties of the bromeliaceae Nidularium procerum: inhibition of eosinophil activation and influx. 1627 31

Myrtaceae is a plant family widely used in folk medicine and Syzygium and Eugenia are among the most important genera. We investigated the anti-allergic properties of an aqueous leaf extract of Syzygium cumini (L.) Skeels (SC). HPLC analysis revealed that hydrolyzable tannins and flavonoids are the major components of the extract. Oral administration of SC (25-100 mg/kg) in Swiss mice (20-25 g; N = 7/group) inhibited paw edema induced by compound 48/80 (50% inhibition, 100 mg/kg; P <or= 0.05) and, to a lesser extent, the allergic paw edema (23% inhibition, 100 mg/kg; P <or= 0.05). SC treatment also inhibited the edema induced by histamine (58% inhibition; P <or= 0.05) and 5-HT (52% inhibition; P <or= 0.05) but had no effect on platelet-aggregating factor-induced paw edema. SC prevented mast cell degranulation and the consequent histamine release in Wistar rat (180-200 g; N = 7/group) peritoneal mast cells (50% inhibition, 1 microg/mL; P <or= 0.05) induced by compound 48/80. Pre-treatment of BALB/c mice (18-20 g; N = 7/group) with 100 mg/kg of the extract significantly inhibited eosinophil accumulation in allergic pleurisy (from 7.662 +/- 1.524 to 1.89 +/- 0.336 x 10(6)/cavity; P <= 0.001). This effect was related to the inhibition of IL-5 (from 70.9 +/- 25.2 to 12.05 +/- 7.165 pg/mL) and CCL11/eotaxin levels (from 60.4 +/- 8.54 to 32.8 +/- 8.4 ng/mL) in pleural lavage fluid, using ELISA. These findings demonstrate an anti-allergic effect of SC, and indicate that its anti-edematogenic effect is due to the inhibition of mast cell degranulation and of histamine and serotonin effects, whereas the inhibition of eosinophil accumulation in the allergic pleurisy model is probably due to an impairment of CCL11/eotaxin and IL-5 production.
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PMID:Pharmacological study of anti-allergic activity of Syzygium cumini (L.) Skeels. 1722 3

Allergic diseases, such as allergic asthma, are hypersensitivity reactions initiated by immunological mechanisms. Myrica esculenta (M. esculenta) is known traditionally in Ayurveda to possess anti-asthmatic activity. The present investigation was undertaken to evaluate the effect of crude extract of stem bark of M. esculenta (Family Myricaceae, commonly known as Kaiphal) on experimental allergic reactions. Experimental models studied were allergic pleurisy and vascular permeability induced by acetic acid in mice. Pretreatment with M. esculenta (75 mg/kg and 150 mg/kg, p.o.) significantly inhibited the eosinophil accumulation (P < 0.01) respectively in the pleural cavity. M. esculenta (75 and 150 mg/kg, p.o.) significantly inhibited the rise in plasma exudation (57.12% and 59.77%, P < 0.01) induced by acetic acid in mice. These findings demonstrate that the crude extract from the stem bark of M. esculenta possesses antiallergic activity. This activity may be mediated by reducing the release of mediators such as histamine, inhibition of mast cell degranulation, and inhibition of eosinophil accumulation thereby preventing the release of cytokines and chemokines.
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PMID:Anti-allergic Activity of Stem Bark of Myrica esculenta Buch.-Ham. (Myricaceae). 2133 Nov 96


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