RESUMO
We previously isolated quercetin 3-O-beta-(2''-galloyl)-glucopyranoside (QG-32) from Persicaria lapathifolia (Polygonacease) as an inhibitor of superoxide production. In the present study, QG-32 was found to inhibit interleukin (IL)-6 production in endotoxin lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7. The QG-32 attenuated LPS-induced synthesis of IL-6 transcript but also inhibited IL-6 promoter activity, indicating that the compound could down-regulate LPS-induced IL-6 expression at the transcription level. Since nuclear factor (NF)-kappaB has been evidenced to play a major mechanism in the LPS-induced IL-6 expression, an effect of QG-32 on NF-kappaB activating pathway was further analyzed. QG-32 inhibited nuclear import as well as DNA binding activity of NF-kappaB complex and subsequently suppressed NF-kappaB transcriptional activity in LPS-stimulated macrophages. However, QG-32 affected neither LPS-induced inhibitory kappaB (IkappaB) degradation nor IkappaB kinase (IKK) activation. In another experiment, QG-32 inhibited expression vector encoding NF-kappaB p65 or p50-elicited IL-6 promoter activity. Taken together, QG-32 could inhibit NF-kappaB-dependent IL-6 expression, targeting nuclear translocation of NF-kappaB complex downstream IkappaB degradation. This mechanism of action would be different from that of quercetin, an aglycone of QG-32, targeting IKK upstream IkappaB degradation. Finally, this study could provide a pharmacological potential of QG-32 in the inflammatory disorders.
Assuntos
Imunossupressores/farmacologia , Interleucina-6/antagonistas & inibidores , Lipopolissacarídeos/antagonistas & inibidores , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , NF-kappa B/antagonistas & inibidores , Quercetina/análogos & derivados , Animais , Linhagem Celular , Ácido Gálico , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Glucosídeos , Interleucina-6/biossíntese , Interleucina-6/genética , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Polygonaceae/imunologia , Quercetina/fisiologiaRESUMO
BACKGROUND: Buckwheat (BW) has been recognized as a common food allergen in Korea, Japan, and other countries. Until now, serologic findings of BW food-allergic patients and its major allergenic components have not been clarified. In this study, we analyzed the serologic findings of BW food allergy and characterized its major allergenic components. METHODS: Nineteen BW-allergic subjects with symptoms after BW ingestion and 15 asymptomatic control subjects with positive skin prick test to BW were recruited. BW-specific IgE was measured with the Pharmacia CAP kit. Allergenic components of BW were analyzed by IgE immunoblotting, periodate oxidation, two-dimensonal PAGE, and sequencing of N-terminal amino acids. RESULTS: From the BW-allergic patients and asymptomatic controls, the sensitivity (100%), specificity (53%), and negative (100%) and positive predictive values (73%) of Pharmacia CAP specific IgE for diagnosis were estimated. The prevalence of IgE binding to 24-kDa (pI 8.3), 16-kDa (pI 5.6), and 9-kDa (pI 5.0/ 6.0) allergens was higher than 50% in BW-allergic and asymptomatic subjects. However, the specific IgE to split 19-kDa (pI 6.5/7.0) allergens were more specifically found in BW-allergic patients than in asymptomatic subjects (78% vs 7%). N-terminal amino-acid sequences of 19-kDa and 16-kDa allergens showed moderate and weak homology to the 19-kDa globulin protein of rice and alpha-amylase/trypsin inhibitor of millet, respectively. The N-terminus of the 9-kDa isoallergens were not different from each other and were identified as the reported trypsin inhibitors of BW. Attenuation of the IgE binding to the 9-kDa allergen was found with periodate oxidation. CONCLUSIONS: The allergens of 24, 19, 16, and 9 kDa are strong candidates to be major allergens, and the 19-kDa allergen was relatively specific for BW-allergic patients. Moreover, measurement of BW-specific IgE and the features of immunoblotting should be very useful tools in the diagnosis of BW allergy.
Assuntos
Alérgenos/análise , Hipersensibilidade Alimentar/etiologia , Polygonaceae/imunologia , Adolescente , Adulto , Alérgenos/química , Sequência de Aminoácidos , Método Duplo-Cego , Feminino , Humanos , Immunoblotting , Imunoglobulina E/sangue , Masculino , Dados de Sequência Molecular , Peso MolecularRESUMO
The field of systemic contact dermatitis is particularly interesting for an allergist. To think of an allergen with cross-reaction and monosensilization should be the first reflex when an enquiry into a skin problem involves an allergic symptom. The three examples quoted involve Peruvian balm as the sensitizing agent. The causal triggering medicines are all vegetal extracts.