Imidacloprid inhibits IgE-mediated RBL-2H3 cell degranulation and passive cutaneous anaphylaxis

BACKGROUND: Imidacloprid has been commonly used as a pesticide for crop protection and acts as nicotinic acetylcholine receptor agonists. Little information about the relationship between imidacloprid and allergy is available. OBJECTIVE: This study aims to examine the effects of imidacoprid on IgE-mediated mast cell activation. METHODS: The rat basophilic leukemia cell line RBL-2H3 (RBL-2H3 cells) were treated with 10⁻³ – 10⁻¹² mol/L imidacloprid, followed by measuring the mediator production, influx of Ca²⁺ in IgE-activated RBL-2H3 cells, and the possible effects of imidacoprid on anti-dinitrophenyl IgE-induced passive cutaneous anaphylaxis (PCA). RESULTS: It was shown that imidacoprid suppressed the production of histamine, β-hexosaminidase, leukotriene C4, interleukin-6, tumor necrosis factor-α, and Ca²⁺ mobilization in IgE-activated RBL-2H3 cells and decreased vascular extravasation in IgE-induced PCA. CONCLUSION: It is the first time to show that imidacloprid suppressed the activation of RBL-2H3 cells.

Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cgamma1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-kappaB pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

Molecular Genetic Mechanisms of Chronic Urticaria

Chronic urticaria (CU) is a common allergic skin disease that requires long-term pharmacological treatment. Some patients with severe CU suffer a poor quality of life. Although the pathogenic mechanisms of CU are not clearly understood, several groups have suggested that genetic mechanisms are involved in various CU cohorts. To further understand the molecular genetic mechanisms of CU, we summarize recent genetic data in this review. Although a few HLA alleles were suggested to be candidate markers in different ethnic groups, further replication studies that apply the recent classification are needed. Genetic polymorphisms in histamine-related genes, including FcepsilonRI and HNMT, were suggested to be involved in mast cell activation and histamine metabolism. Several genetic polymorphisms of leukotriene-related genes, such as ALOX5, LTC4S, and the PGE2 receptor gene PTGER4, were suggested to be involved in leukotriene overproduction, a pathogenic mechanism. Further investigations using candidate gene approaches and genome-wide association studies (GWAS) will provide new insights into the molecular genetic mechanisms of CU, which will provide new marker genes for differentiation of CU phenotypes and identification of potential therapeutic targets.

Curcumin Inhibits the Activation of Immunoglobulin E-Mediated Mast Cells and Passive Systemic Anaphylaxis in Mice by Reducing Serum Eicosanoid and Histamine Levels

Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2) and 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular Ca2+ influx via phospholipase Cgamma1 (PLCgamma1) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappaB (NF-kappaB) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum LTC4, PGD2, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.

Curcumin Inhibits the Activation of Immunoglobulin E-Mediated Mast Cells and Passive Systemic Anaphylaxis in Mice by Reducing Serum Eicosanoid and Histamine Levels

Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2) and 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular Ca2+ influx via phospholipase Cgamma1 (PLCgamma1) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappaB (NF-kappaB) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum LTC4, PGD2, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.

Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway

The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of PGD2 and LTC4 in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase Cgamma1 (PLCgamma1)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase and p38), and the nuclear factor-kappaB (NF-kappaB) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.

The anti-inflammatory effect of Cheongseoikki-tang ethanol extract on allergic reactions mediated by bone marrow-derived mast cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>Cheongseoikki-tang (CIT, Korean), also called Qingshu Yiqi decoction () and Seisho-ekki-to (Japanese), is well known as an effective traditional combination of herbs for treating cardiovascular diseases. This study was to research its effects on bone marrow-derived mast cell (BMMC)-mediated allergy and inflammation mechanisms.</p><p><b>METHODS</b>In this study, the biological effect of Cheongseoikki-tang ethanol extract (CITE) was evaluated, focusing on its effects on the production of allergic mediators by phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-stimulated BMMCs. These allergic mediators included interleukin-6 (IL-6), prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and β-hexosaminidase (β-hex).</p><p><b>RESULTS</b>Our data revealed that CITE inhibited the production of IL-6, PGD2, LTC4, and β-hex induced by PMA plus A23187 (P<0.05).</p><p><b>CONCLUSION</b>These findings indicate that CITE has the potential for use in the treatment of allergy.</p>

Multidrug resistance associated proteins in multidrug resistance / 癌症

Multidrug resistance proteins (MRPs) are members of the C family of a group of proteins named ATP-binding cassette (ABC) transporters. These ABC transporters together form the largest branch of proteins within the human body. The MRP family comprises of 13 members, of which MRP1 to MRP9 are the major transporters indicated to cause multidrug resistance in tumor cells by extruding anticancer drugs out of the cell. They are mainly lipophilic anionic transporters and are reported to transport free or conjugates of glutathione (GSH), glucuronate, or sulphate. In addition, MRP1 to MRP3 can transport neutral organic drugs in free form in the presence of free GSH. Collectively, MRPs can transport drugs that differ structurally and mechanistically, including natural anticancer drugs, nucleoside analogs, antimetabolites, and tyrosine kinase inhibitors. Many of these MRPs transport physiologically important anions such as leukotriene C4, bilirubin glucuronide, and cyclic nucleotides. This review focuses mainly on the physiological functions, cellular resistance characteristics, and probable in vivo role of MRP1 to MRP9.

Effects of polydatin on bleomycin-induced pulmonary fibrosis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effects of three different doses of polydatin (PD) on pulmonary interstitial fibrosis in rats induced by bleomycin.</p><p><b>METHOD</b>One hundred and twenty-nine healthy Sprague-Dawley rats three months old, were randomly divided into six groups. Group A: normal control group; group B: model group treated with bleomycin (pretreatment with saline 1 mL x kg(-1) intraperitoneally before bleomycin); group C: PD 10 mg x kg(-1) (pretreatment with PD 10 mg x kg(-1) intraperitoneally before bleomycin); group D: PD 20 mg x kg(-1) (pretreatment with PD 20 mg x kg(-1) intraperitoneally before bleomycin); group E: PD 40 mg x kg(-1) (pretreatment with PD 40 mg x kg(-1) intraperitoneally before bleomycin), group F: dexamethason (DXM) treated group (pretreatment with saline 1 mL x kg(-1) intraperitoneally before bleomycin and then with DXM 1 mg x kg(-1) x d(-1)). At day 3, 7, 14, 28 after injection of bleomycin, eight rats in each group were randomly chosen to be killed. The right lungs of dead rats were removed and appropriately processed for hematoxylin and eosin (H&E) stain, histologically observed under light microscope. The hydroxyproline content and the PLA2 activity in pulmonary homogenate were measured with alkaline hydrolysis assay and acid modified microtitrimetic method. The levels of leukotriene C4 (LTC4), prostaglandin E2 (PGE2), transforming growth factor-beta1 (TGF-beta1) in bronchoalveolar lavage fluid (BALF) were measured with enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULT</b>At day 3, 7, 14, 28 after intratracheal instillation of bleomycin in rats of group B, the PLA2 activity in lung homogenate and the levels of its metabolic products PGE2, LTC4 as well as TGF-beta1 in BALF increased significantly compared with those in group A (P < 0.01). And lung hydroxyproline concentration began to grow up markedly at day 7 compared with those in group A (P < 0.05), reaching its maximum at day 28. Compared with group B, three different doses of PD and DXM significantly reduced the activity of the PLA2 and hydroxyproline concentration in lung homogenate as well as the levels of PGE2, LTC4, TGF-beta1 in BALF at various periods (P < 0.05). There was statistically significant difference between three different doses of PD groups (P < 0.05). And the group E (PD 40 mg x kg(-1)) was lower than group D (PD 20 mg x kg(-1)), group D was lower than group C (PD 10 mg x kg(-1)) (respectively, P < 0.01). Group E and DXM group were no significant difference. However, all these observation parameters were higher than the normal level (compared with group A, P < 0.01). Histological studies revealed that it was showed less inflammation and a lower degree of fibrosis in the lungs treated with PD than bleomycin model group.</p><p><b>CONCLUSION</b>PD has the protective effect on pulmonary interstitial fibrosis. However, it can't completely block the process of pulmonary fibrosis.</p>

Association study of polymorphism in leukotriene C4 synthase and cysteinyl leukotriene receptor 1 genes with phenotype of asthma and clinical parameters in Korean children / 소아과

PURPOSE: Cysteinyl leukotrienes are important proinflammatory mediators in asthma. Recently, it was suggested that a promoter polymorphism in the genes encoding for leukotriene C4 synthase (LTC4S), a key enzyme in the leukotriene synthetic pathway, and cysteinyl leukotriene receptor 1 (CysLTR1) might be associated with aspirin-intolerant asthma. We investigated whether polymorphisms in LTC4S and CysLTR1 genes or their interactions were associated with the asthma phenotype, lung function, or bronchial hyperreactivity (BHR) in Korean children. METHODS: A total of 856 asthmatic children and 254 non-asthmatic controls were enrolled; a skin prick test, lung function test and bronchial provocation test were performed. Of those enrolled, 395 children underwent exercise challenge tests. The LTC4S A(-444)C and CysLTR1 T(+927)C were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Of those enrolled, 699 children were classified as having atopic asthma and 277 children, as having exercise-induced asthma (EIA). LTC4S and CysLTR1 polymorphisms were not associated with atopic asthma, EIA, or asthma per se. Lung function and BHR were not significantly different between the wild type (AA or TT) and the variant (AC+CC or TC+CC) genotypes in asthmatics, atopic asthmatics, and EIA (+) asthmatics, while total eosinophil counts were higher in the variant type of LTC4S than in the wild type in atopic asthmatics. There were no associations between the gene-gene interactions of LTC4S and CysLTR1 genotypes and the asthma phenotypes. CONCLUSION: LTC4S A(-444)C and CysLTR1 T(+927)C polymorphisms and their gene-gene interactions are not associated with asthma phenotype, lung function, or BHR in Korean children.

Effects of ATP and LTC4 on hypoxic pulmonary vasoconstriction in isolated rat lungs / 대한마취과학회지

BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) is unique to pulmonary circulation but the mechanism remains elusive. Red blood cells (RBCs) are known to augment HPV and to release more ATP as oxygen content falls. Leukotrienes constrict smooth muscle and could be important for the regulation of the pulmonary circulation. Hence we hypothesized that ATP and leukotrienes are mediators of HPV produced during acute alveolar hypoxia. METHODS: In forty Sprague-Dawley rats, lungs were isolated and perfused. We administered ATP (10 micrometer) to the ATP group (n = 8), the ATP antagonist, suramin (100 micrometer) to the suramin group (n = 8), leukotriene C4 (LTC4, 5 microgram) to the LTC4 group (n = 8), the LTC4 antagonist, LY171883 (20 micrometer) to the LY171883 group (n = 8), and LTC4 (5 microgram) + ATP (10 micrometer) to the LTC4 + ATP group (n = 8) during normoxic ventilation. HPV responses were induced by three hypoxic challenges for 5 minutes separated by 5 minutes of ventilation with a normoxic gas mixture. Baseline pulmonary artery pressure change after exposure to each drug and hypoxic pressor response between a period 21% normoxic gas ventilation and that of 3% hypoxic gas ventilation were measured. RESULTS: ATP and LTC4 + ATP increased baseline pulmonary artery pressures but LTC4 did not alter it. ATP did not affect hypoxic pressor response. Suramin, LY171883 and LTC4 + ATP inhibited the pressor response to hypoxia. LTC4 increased hypoxic pressor response. CONCLUSIONS: In isolated rat lungs, HPV may be mediated by ATP and LTC4 appears more likely to be a modulator than a mediator of HPV.

Effects of among compositions of Herba Ephedrae decoction on genic xpression of 5-lipoxygenase activating protein, IL-4 and leukotriene C4 in asthmatic mice / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the regularity of recipe composition by observing inhibitory effects on the genic expression of 5-lipoxygenase activating protein, IL-4 and the leukotriene C4 in asthmatic mice.</p><p><b>METHOD</b>The mice were challenged with OVA and administered ig with the Herba Ephedrae decoction (HED), separated compositions (2500 mg x kg(-1), calculated by Herba Ephedrae) and dexamethasone (2 mg x kg(-1)) respectively once daily for seven days. The real-time fluorescence quantitative PCR method was employed to measure the contents of FLAP mRNA and IL-4 mRNA expressions in lung and the ELISA method was used to determine the content of LTC4 in the washing solution of pulmonary alveolus and bronchi.</p><p><b>RESULT</b>In the lung of asthma mice, the expressions of FLAP and IL-4 and the content of LTC4 were significantly augmented compared with the control group. The HED and the separated compositions could suppress the expressions of FLAP and IL-4 and LTC4 release to a great extent in mice.</p><p><b>CONCLUSION</b>The HED had the remarkable effects of antianaphylaxis asthma and the original formula HED worked best. These results confirmed the rationality and scientific level of HED.</p>

Effect of shuanglong capsule on content of leukotrienes compound of lung tissues in asthmatic rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the changing contents of leukotriene B4 ( LTB4 ), leukotriene C4 ( LTC4 ), and leukotriene D4 (LTD4 ) of lung tissue in asthmatic rats, and explore the effect of Shuanglong Capsule (SLC) on it.</p><p><b>METHODS</b>SD rats were randomly divided into the nomal group, asthmatic model group, Dexamethasone group and the high, middle and low dose SLC groups. All rats except those in the normal group were sensitized by ovalbumin and challenged with the antigen, and the contents of LTB4, LTC4 and LTD4 in lung tissue of all the groups were measured by reverse phase-high performance liquid chromatography (RP-HPLC) and compared.</p><p><b>RESULTS</b>The levels of LTB4, LTC4, and LTD4 of asthmatic rats were significantly higher than those of rats in the normal group. Dexamethasone and SLC at the dose of 8. 27 g/kg or 4. 13 g/kg could significantly inhibit the production of leukotrienes of lung tissue in asthmatic rats (P <0.05).</p><p><b>CONCLUSION</b>SLC can significantly inhibit the formation of inflammatory medium LTs of lung tissue in asthmatic rats, it may be one of the key mechanisms of SLC in anti-asthma and anti-inflammatory action.</p>

Eficácia do montelucaste na prevenção da urticária e angioedema desencadeados pelo ácido acetil-salicílico em pacientes a ele intolerantes / Efficacy af mantelukast in the preventian af acetylsalicylic acid induced urticaria and angiaedema in intalerant patients

Objetivo: determinar a eficácia do Montelucaste (MK) na inibição das reações cutâneas induzidas pelo ácido acetil-salicílico (AAS) em pacientes a ele intolerantes.Método: participaram do estudo crianças e adolescentes, maiores de seis anos, com histórico de reação prévia ao AAS comprovada por teste de provocação oral (TPO). Foram excluídos pacientes em uso crônico de antihistamínicos e os com relato prévio de anafilaxia ou de reação grave. Todos foram submetidos a novo TPO com AAS 24 horas após introdução de MK (TPO-MK). Os TPO foram realizados em ambiente hospitalar, de forma simples cega e controlados com placebo. Os TPO-MK foram realizados em dois dias consecutivos: no primeiro dia receberam placebo e a primeira dose de MK (5 ou 10mg) e no segundo dia AAS (100, 250 e 500mg a cada duas horas) e a segunda dose de MK. Os dados obtidos no TPO-MK foram comparados aos do TPO anterior (TPO-B). Resultados: Inibição total de reações adversas foi observado em 2/8 (25%) casos. Em comparação com os TPO-B, os pacientes submetidos aos TPO-MK tiveram duração das reações cutâneas significantemente menor (mediana: 2,5 vs 1,75 horas; p=0,04), retardo de início (mediana: 1,85 vs 3,25 horas; p=O,03) e desencadeamento com dose maior de AAS (mediana: 100 vs 350mg; p=0,04). Houve, também, menor necessidadede administração de medicação para controle das reações. Conclusões: apesar de minorar as reações adversas em pacientes com urticária/angioedema induzidos por AAS, o uso de MK inibiu completamente tais reações apenas em parcela deles. Os resultados sugerem que os leucotrienos cisteínicos, apesar de desempenharem importante papel, não são os únicos mediadores envolvidos nas reações cutâneas ao AAS.

Association of Leukotriene C4 Synthase Gene Polymorphism with Clinical Response to Montelukast in Childhood Asthma / 소아과

PURPOSE: Cysteinyl leukotrienes are important inflammatory mediators in the pathogenesis of asthma; therefore interruption of cysteinyl leukotrienes by leukotriene receptor antagonists improves clinical symptoms in the management of patients with mild to moderate asthma. We evaluated whether clinical response to montelukast, a leukotriene receptor antagonist, in childhood asthma was predicted by genotypes of leukotriene C4 synthase (LTC4S) promoter gene polymorphism. METHODS: An 8-week prospective, open trial of montelukast was carried out in 161 children with mild to moderate asthma. Genotyping of LTC4S gene polymorphism was determined by restriction fragment length polymorphism. RESULTS: The distribution of the LTC4S genotypes AA, AC, and CC was 70.8 percent, 23.6 percent, and 5.6 percent, respectively in asthma group and 74.0 percent, 22.6 percent, and 3.4 percent, respectively in control group. A statistically significant difference in the distribution of LTC4S genotype was not observed between the asthma and the control groups, and there was no significant difference between the LTC4S genotype and asthma severity. The responders to montelukast were significantly prevalent in the mild asthma group (P< 0.05). There was no significant difference in the distribution of the responders compared to non-responders within genotype in the total asthma group or the moderate asthma group. However, the responsiveness for montelukast was significant difference within genotype for both AA and AC/CC in the mild asthma group: The AA genotype was more included in the responder group (P< 0.05). CONCLUSION: In the mild persistent asthma group, the A allele of LTC4S polymorphism may be regarded as a predictable factor for clinical response to montelukast. However, LTC4S polymorphism was not significantly associated with the clinical response to montelukast in asthmatic children.

effect of acetylsalicylic acid on the release rates of leukotrienes B4 and C4 from cultured skin melanocytes of active vitiligo

The aim of this study is to investigate the effect of the non-steroidal anti-inflammatory agent, acetylsalicylic acid [ASA], otherwise known as aspirin, at different concentrations on the release rates of the pro-inflammatory mediators, leukotriene B4 [LTB4] and leukotriene C4 [LTC4] from in vitro cultured melanocytes obtained from normal pigmented skin of patients with active vitiligo. This study was carried out between April, 2000 and September, 2001, at The Vitiligo Unit, King Abdul-Aziz University Medical Center, Jeddah, Kingdom of Saudi Arabia. Skin biopsies were obtained from patients with active vitiligo [n=7] of different extent and duration, and normal healthy age-matched individuals [n=7] serving as control were recruited to the study. The release rates of LTB4 and LTC4 were determined before and after the addition of the ASA at 3 different concentrations [15, 75, 150 ug/ml] in the primary skin melanocytes culture medium using a commercially available kit based on radioimmunoassay method. Following the ASA treatment at 3 different concentrations [15, 75 and 150 ug/ml], the release rates of LTB4 and LTC4 were increased from melanocytes of the normal individuals [13%, 7.5% and 30%; 7.2%, 51.4% and 60.7%, p<0.001]. However, in patients with active vitiligo, the release rate of LTB4 from melanocytes was decreased [2.9%, 14.4% and 7.4%, p<0.05], whereas that of LTC4 was increased [3.9%, 93.8% and 101.4%, p<0.001]. Acetylsalicylic acid at therapeutic concentrations can regulate the release rates of LTB4 and LTC4 from cultured skin melanocytes of normal and active vitiligo subjects

Leukotriene related gene polymorphisms in ASA-intolerant asthma: an association of 5-lipoxygenase haplotype / 천식및알레르기

BACKGROUND AND OBJECTIVES: A recent study has demonstrated a possible involvement of leukotriene C4 synthase (LTC4S) gene polymorphism in ASA-intolerant asthma (AIA) in a Polish population, while no significances were noted in other populations. To investigate the role of genetic polymorphism in AIA development, we screened single nucleotide polymorphisms (SNPs) for the key enzymes involved in arachidonate metabolism, and cysteinyl leukotriene receptor 1 (CYSLTR1) in a larger scale of Korean population with AIA. MATERIALS AND METHODS: 93 AIA and 181 ASA-tolerant asthma (ATA) patients, and 123 normal controls (NC) were enrolled. Single base extension method was applied for genotyping of SNPs in 5-lipoxygenase (ALOX5, -1708G>A, 21C>T, 270G>A, 1728G>A), ALOX5 activating protein (FLAP, 218A>G), cyclooxygenase 2 (COX2, -162C>G, 10T>G, 228G>A), LTC4S (-444A>C), and CYSLTR1 (927T>C). Haplotype analyses for ALOX5 were performed as well. RESULTS: There were no significant differences in allele and genotype frequencies of the SNPs among the three groups (p>0.05). However, the frequency of ALOX5-ht1[G-C-G-A] containing genotype in the AIA group was significantly higher than those of the ATA group (p=0.01, OR =5.0, 95%CI=1.54-17.9) and the normal controls (p=0.03, OR=4.5, 95%CI=1.1-18.4) with a dominant model. CONCLUSION: These results suggest a lack of association between FLAP, COX2, LTC4S, and CYSLTR1 gene polymorphisms, and AIA phenotype in Korean population. However, a possible involvement of ALOX5-ht1[G-C-G-A] in AIA development was suggested.

Antagonism of sophoricoside from sophorica japonica on GM-CSF-induced cosinophil activation / 천식및알레르기

BACKGROUND: allergic disease is an inflammatory disease, whose main inflammatory cells are eosinophils, mast cells, and T lymphocytes. From that point, new therapeutic targets on allergic inflammation focusing on them are under investigation. We extracted four isoflavonoids from sophorica japonica such as sophi, orobol, genistin and genistein which are known PTK antagonists. We documented that these iso-flavonoids except genistein had an antagonism on IL-5 and IL-3 in vitro eosinophil activation and also in allergic mouse model sensitized by OA(ovualbumin). Their common action is due to the common beta chains. GM-CSF also share common beta chains, through which it activates eosinophils. OBJECTIVES: From the above results, We observed the antagonistic effects of these compounds on GM-CSF using eosinophil activation in vitro. METHODS: LTC4 which was detected by RIA and ECP by UniCAP were activation markers. RESULTS: Among those compounds, sophi was the most potent antagonist on GM-CSF induced LTC4 release and even on degranulation and orobol and genistin also had antagonism on them but genistein an antagonist of PTK did not show any antagonistic effects. CONCLUSION: From these results, We concluded these three iso-flavonoids were GM-CSF antagonists and the mechanism might not be through PTK signaling.

Inhibition of Cryptoporus volvatus ferment substance on release of leukotriene B4, C4 and D4 from neutrophils in rats in vitro / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study inhibitory the effects of Cryptoporus volvatus ferment substance(CVFS) on leukotriene production in vitro from neutrophils in rats.</p><p><b>METHODS</b>Neutrophil aggregation was induced by intraperitoneal injection of glycogen in rats. After 16 h, intraperitoneal lavage fluid(PLF) was collected and neutrophils were removed. Neutrophils were stimulated by calcium ionophore A23187 in vitro to produce leukotriene B(4), C(4), D(4). The concentrations of leukotriene B(4), C(4) and D(4) were measured by reversed-phase high-performance liquid chromatography(HPLC).</p><p><b>RESULT</b>CVFS at 0.25, 1, 4 mg x L(-1)decreased leukotriene B(4), C(4), D(4) release from neutrophils in a concentration-dependent manner. Inhibitory rate of CVFS 0.25, 1, 4 mg x L(-1 )on A23187-induced leukotriene B(4) production was 27.4%, 54.2% and 78.8%(P<0.05), respectively. Inhibitory rate of leukotriene C(4) production was 65.1%, 74.3 and 79.0%(P<0.05), respectively. Inhibitory rate of leukotriene D(4) production was 55.6%, 60.9% and 72.8%(P<0.05), respectively.</p><p><b>CONCLUSION</b>The results suggest that suppression of leukotriene release may be a mechanism of the anti-inflammation and anti-asthma effects of CVFS.</p>