interleukin-8 and santin

Propolis is a bee product used in folk medicine to treat inflammatory diseases. Diverse types of propolis are produced worldwide depending on the local flora. Recently, research has been focused on a propolis sample produced in the northeast Brazilian "caatinga" from Mimosa tenuiflora, popularly known as "jurema-preta".. A possible immunomodulatory/anti-inflammatory action was analyzed to verify the potential of M. tenuiflora propolis (MP) and its constituents (santin, sakuranetin and kaempferide) in human immune cells under baseline conditions or in LPS-stimulated cells.. Cell viability, cytokine (TNF-α, IL-1β, IL-6, IL-8, IL-10) production and intracellular pathways (NF-kB and p38 MAPK) were evaluated.. Under basal conditions, MP and sakuranetin did not affect cytokine production; santin enhanced TNF-α, IL-1β, IL-6, while kaempferide inhibited IL-8 and IL-10. In LPS-stimulated cells, MP and its compounds exerted an inhibitory activity on TNF-α and IL-1β, while no effects were seen on IL-6 and IL-8. Santin and kaempferide inhibited IL-10 production. No significant differences were seen on NF-kB and p38 MAPK intracellular pathways.. Data indicated the immunomodulatory action of caatinga propolis and its constituents at noncytotoxic concentrations, specifically an anti-inflammatory activity in LPS-treated cells by inhibiting cytokine production. Santin, sakuranetin and kaempferide appeared to be involved in MP activities.

Topics: Anti-Inflammatory Agents; Cytokines; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Lipopolysaccharides; Mimosa; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Propolis; Tumor Necrosis Factor-alpha

Enterotoxin produced by enterotoxigenic Bacteroides fragilis (BFT) has been associated with mucosal inflammation and diarrhoeal diseases. In this study, the anti-inflammatory molecular mechanism of 5,7-dihydroxy-3,4,6-trimethoxyflavone (eupatilin) was characterized in an HT-29 intestinal epithelial cell line stimulated with BFT. Pre-treatment of HT-29 cells with eupatilin decreased the production significantly of both interleukin (IL)-8 and prostaglandin E(2) induced by BFT in a dose-dependent manner. BFT-activated nuclear factor-kappaB (NF-kappaB) signals in HT-29 cells and pretreatment with eupatilin suppressed NF-kappaB activation that resulted in the significant inhibition of IL-8 and cyclo-oxygenase-2 expression. BFT-induced phosphorylation of both I kappaB alpha and I kappaB kinase (IKK) signals was prevented in eupatilin-pretreated HT-29 cells. Transfection of siRNA for IKK-alpha and IKK-beta decreased the production of IL-8 and prostaglandin E(2); however, the transfection of IKK-beta siRNA showed a more significant reduction of BFT-induced I kappaB alpha phosphorylation compared with that of IKK-alpha siRNA. In addition, herbimycin A, a specific inhibitor of heat shock protein 90 (Hsp90), decreased the BFT-induced activation of IKK and NF-kappaB, suggesting that Hsp90 is associated with a pathway of IKK-NF-kappaB-IL-8/cyclo-oxygenase-2 gene signalling. Furthermore, eupatilin dissociated the complex between Hsp90 and IKK-gamma in BFT-stimulated HT-29 cells. These results suggest that eupatilin can suppress the NF-kappaB signalling pathway by targeting the Hsp90-IKK-gamma complex in intestinal epithelial cells and may attenuate BFT-induced inflammatory responses.

Topics: Animals; Anti-Inflammatory Agents; Bacteroides fragilis; Chemokine CXCL2; Cyclooxygenase 2; Electrophoretic Mobility Shift Assay; Enterotoxins; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Flavonoids; HSP90 Heat-Shock Proteins; HT29 Cells; Humans; I-kappa B Kinase; I-kappa B Proteins; Ileum; Immunoprecipitation; Interleukin-8; Intestinal Mucosa; Mice; NF-kappa B; NF-KappaB Inhibitor alpha; Reverse Transcriptase Polymerase Chain Reaction