RESUMO
This work intends to perform a comparative study on the allergenic potential of ß-lactoglobulin (BLG)-glucose, BLG-caffeic acid and BLG-caffeoyl glucopyranose conjugates. The modifications changed the molecular weight and multi-structure of BLG and destroyed the allergenic epitope, which resulted in a decrease in the IgE binding level and the release ability of histamine and IL-6 in KU812 cells. Compared with BLG, the conjugates reduced the serum levels of IgG, IgE, ß-Hex and IL-4 in vivo, while increasing the level of interferon-γ, which caused an imbalance of Th1/Th2 immune response. Meanwhile, these conjugates not only increased the relative abundance of allergy-related gut flora, such as Lachnospiraceae, norank_o_Clostridia_UCG-014, Erysipelotrichaceae, Turicibacter and Lachnospiraceae_NK4A136_group, but also improved the level of short-chain fatty acids (SCFAs). Caffeoyl glucopyranose with a large molecular weight and long carbon chains exerted a great influence on the allergy-related gut flora and SCFAs. Therefore, the changes in the Th1/Th2 balance and SCFA level produced by the allergy-related gut flora were responsible for reducing the potential allergy of BLG.
Assuntos
Alérgenos , Hipersensibilidade , Humanos , Glucose , Lactoglobulinas , Imunoglobulina ERESUMO
BACKGROUND: Angiogenesis plays an important role in the development of rheumatoid arthritis (RA), which increases the supply of nutrients, cytokines, and inflammatory cells to the synovial membrane. Genistein (GEN), a soy-derived isoflavone, has been validated that can effectively inhibit the angiogenesis of several tumours. We thus carried out a study in vitro to investigate the effect of GEN in vascular endothelial growth factor (VEGF) expression and angiogenesis induced by the inflammatory environment of RA. METHODS: MH7A cells were used to verify whether GEN can inhibit the expression of VEGF in MH7A cells under inflammatory conditions and demonstrate the mechanism. EA.hy926 âcells were used to verify whether GEN can inhibit the migration and tube formation of vascular endothelial cells in inflammatory environment. RESULTS: GEN dose-dependently inhibited the expression and secretion of interleukin (IL)-6 and VEGF, as well as the nucleus translocation of Signal transducer and activator of transcription 3 (STAT3) in MH7A. Furthermore, GEN inhibited IL-6-induced vascular endothelial cell migration and tube formation in vitro. CONCLUSION: GEN inhibits IL-6-induced VEGF expression and angiogenesis partially through the Janus kinase 2 (JAK2)/STAT3 pathway in RA, which has provided a novel insight into the antiangiogenic activity of GEN in RA. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study provides scientific guidance for the clinical translational research of GEN in the RA treatment.