interleukin-8 and kaempferol

Inflammation induced by Helicobacter pylori infection related to gastric carcinogenesis. In this study, we have investigated the anti-inflammatory effect and its mechanism of kaempferol in the inflammatory response caused by H. pylori infection in vitro. We found that kaempferol reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-8) and production of IL-8 in AGS cells. In addition, kaempferol suppressed translocation of cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) of H. pylori to AGS cells. It was due to decreased transcription of type IV secretion system (T4SS) components involved in CagA injection and secretion system subunit protein A (SecA) of type V secretion system (T5SS) involved in VacA secretion by kaempferol. In conclusion, kaempferol shows the anti-inflammatory effect by suppressing the translocation of CagA and VacA proteins and leading to the down-regulation of pro-inflammatory cytokines. Abbreviations: CagA: cytotoxin-associated gene A; VacA: vacuolating cytotoxin A; T4SS: type IV secretion systems; SecA: secretion system subunit protein A; T5SS: type V secretion system.

Topics: Anti-Inflammatory Agents; Antigens, Bacterial; Bacterial Proteins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-8; Kaempferols; Protein Transport; Transforming Growth Factor alpha

Kaempferol possesses a wide range of therapeutic properties, including antioxidant, anti-inflammatory, and anticancer properties. The present study sought to evaluate the effects and possible pharmacological mechanisms of kaempferol on interleukin (IL)-32-induced monocyte-macrophage differentiation. In this study, we performed flow cytometry assay, immunocytochemical staining, quantitative real-time PCR, enzyme-linked immuno sorbent assay, caspase-1 assay, and Western blotting to observe the effects and underlying mechanisms of kaempferol using the human monocyte cell line THP-1. The flow cytometry, immunocytochemical staining, and real-time PCR results show that kaempferol attenuated IL-32-induced monocyte differentiation to product macrophage-like cells. Kaempferol decreased the production and mRNA expression of pro-inflammatory cytokines, in this case thymic stromal lymphopoietin (TSLP), IL-1β, tumor necrosis factor (TNF)-α, and IL-8. Furthermore, kaempferol inhibited the IL-32-induced activation of p38 and nuclear factor-κB in a dose-dependent manner in THP-1 cells. Kaempferol also ameliorated the lipopolysaccharide-induced production of the inflammatory mediators TSLP, IL-1β, TNF-α, IL-8, and nitric oxide of macrophage-like cells differentiated by IL-32. In brief, our findings may provide new mechanistic insights into the anti-inflammatory effects of kaempferol.

Topics: Anti-Inflammatory Agents; Caspase 1; Cell Differentiation; Cell Line; Cytokines; Humans; Interleukin-8; Interleukins; Kaempferols; Lipopolysaccharides; Macrophages; Microscopy, Confocal; Monocytes; NF-kappa B; Nitric Oxide; p38 Mitogen-Activated Protein Kinases; Real-Time Polymerase Chain Reaction; RNA, Messenger; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor-alpha

This study is to investigate the inhibitory effect of kaempferol on inflammatory response of lipopolysaccharide(LPS)-stimulated HMC-1 mast cells. The cytotoxicity of kaempferol to HMC-1 mast cells were analyzed by using MTT assay and then the administration concentrations of kaempferol were established. Histamine, IL-6, IL-8, IL-1β and TNF-α were measured using ELISA assay in activated HMC-1 mast cells after incubation with various concentrations of kaempferol (10, 20 and 40 µmol.L-1). Western blot was used to test the protein expression of p-IKKβ, IκBα, p-IκBα and nucleus NF-κB of LPS-induced HMC-1 mast cells after incubation with different concentrations of kaempferol. The optimal concentrations of kaempferol were defined as the range from 5 µmol.L-1 to 40 µmol.L-1. Kaempferol significantly decreased the release of histamine, IL-6, IL-8, IL-1β and TNF-α of activated HMC-1 mast cells (P<0.01). After incubation with kaempferol, the protein expression of p-IKKβ, p-IKBa and nucleus NF-κB (p65) markedly reduced in LPS-stimulated HMC-1 mast cells (P<0.01). Taken together, we concluded that kaempferol markedly inhibit mast cell-mediated inflammatory response. At the same time, kaempferol can inhibit the activation of IKKβ, block the phosphorylation of IκBα, prevent NF-KB entering into the nucleus, and then decrease the release of inflammatory mediators.

Topics: Cells, Cultured; Histamine; Humans; I-kappa B Kinase; I-kappa B Proteins; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Kaempferols; Lipopolysaccharides; Mast Cells; NF-kappa B; NF-KappaB Inhibitor alpha; Tumor Necrosis Factor-alpha

Kaempferol (KP) is a major compound of Naju Jjok (Polygonum tinctorium Lour.). The effect of KP on allergic rhinitis (AR) has not been elucidated. Here, we report the effects and mechanisms of KP on new and predominant mediators of AR using an eosinophil cell line, Eol-1 and an ovalbumin (OVA)-induced AR mouse model. KP significantly inhibited the production of interleukin (IL)-32 and IL-8 and activation of caspase-1 in Eol-1 cells. Allergic symptoms and predominant mediators (IgE and histamine) in the KP-administered group were significantly lower than in the AR group. The levels of interferon-γ were enhanced while the levels of IL-4 were reduced in the KP group. KP significantly reduced the levels of IL-32 and thymic stromal lymphopoietin (TSLP) compared with the AR mice. KP reduced the levels of inflammation-related proteins. In the KP-administered groups, the infiltrations of eosinophils and mast cells increased by OVA were decreased. In addition, KP significantly reduced caspase-1 activity in nasal mucosa tissue of AR mice. Our findings indicate that KP has an anti-allergic effect through the regulation of the production of IL-32 and TSLP and caspase-1 activity in allergic diseases including AR.

Topics: Animals; Anti-Allergic Agents; Caspase 1; Cell Line; Cytokines; Disease Models, Animal; Enzyme Activation; Eosinophils; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Histamine; Humans; Immunoglobulin E; Interleukin-4; Interleukin-8; Interleukins; Kaempferols; Mast Cells; Mice; Mice, Inbred BALB C; Organ Size; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Spleen; Thymic Stromal Lymphopoietin

Thermal burn injury induces inflammatory cell infiltrates in the dermis and thickening of the epidermis. Following a burn injury, various mediators, including reactive oxygen species (ROS), are produced in macrophages and neutrophils, exposing all tissues to oxidative injury. The anti-oxidant activities of flavonoids have been widely exploited to scavenge ROS. In this study, we observed that several flavonoids-kaempferol, quercetin, fisetin, and chrysin-inhibit LPS-induced IL-8 promoter activation in RAW 264.7 cells. In contrast with quercetin and fisetin, pretreatment of kaempferol and chrysin did not decrease cell viability. Inflammatory cell infiltrates in the dermis and thickening of the epidermis induced by burn injuries in mice was relieved by kaempferol treatment. However, the injury was worsened by fisetin, quercetin, and chrysin. Expression of TNF-a induced by burn injuries was decreased by kaempferol. These findings suggest the potential use of kaempferol as a therapeutic in thermal burn-induced skin injuries. [BMB reports 2010; 43(1): 46-51].

Topics: Animals; Burns; Cell Differentiation; Cell Line, Tumor; Flavonoids; Flavonols; Interleukin-8; Kaempferols; Lipopolysaccharides; Mice; Quercetin; Reactive Oxygen Species; Skin; Tumor Necrosis Factor-alpha

We investigated the inhibitory effects of quercetin and kaempferol treatment on the suppression of immunoglobulin E (IgE)-mediated allergic responses in relation to intestinal epithelium barrier function in RBL-2H3 and Caco-2 cells.. RBL-2H3 cells as a model of intestinal mucosa mast cells were treated with flavonols followed by IgE-anti-dinitrophenyl sensitization. The extent of degranulation and the release of pro-inflammatory cytokines were measured. Caco-2 cells were stimulated with interleukin (IL)-4 or IgE-allergen with or without flavonol pretreatment and changes in the expression of CD23 mRNA and mitogen-activated protein kinase (MAPK), and chemokine release were determined.. Flavonols inhibited the secretion of allergic mediators in RBL-2H3 cells and suppressed the CD23 mRNA expression and p38 MAPK activation in IL-4 stimulated Caco-2 cells. Flavonols also suppressed IgE-OVA induced extra signal-regulated protein kinase (ERK) activation and chemokine release.. Quercetin and kaempferol effectively suppressed the development of IgE-mediated allergic inflammation of intestinal cell models.

Topics: Animals; Antioxidants; Caco-2 Cells; Chemokine CCL20; Extracellular Signal-Regulated MAP Kinases; Food Hypersensitivity; Humans; Hypersensitivity; Immunoglobulin E; Inflammation; Interleukin-8; Intestinal Mucosa; Kaempferols; Molecular Structure; p38 Mitogen-Activated Protein Kinases; Quercetin; Receptors, IgE

There is increasing evidence that daily intake of flavonoids reduced severity and prevalence of allergic diseases. However, the mechanism of its antiinflammatory effects in allergic diseases remains uncertain. Kaempferol, which belongs to the flavone group, is a strong antioxidant among natural flavonoids and is the essential component of many beverages and vegetables. Because chemokine is one of the key mediators in allergic inflammatory process, we investigated the effect of kaempferol on chemokines expression in monocytes. Our data demonstrated that kaempferol significantly inhibited the lipopolysaccharide (LPS)-induced production of monocyte-derived chemokine (MDC), interferon gamma-induced protein 10 (IP-10), and interleukin-8 (IL-8) in THP-1 cells. Growth-related oncogene-α (GRO-α) was also suppressed at a higher concentration. We also found that kaempferol was able to suppress LPS-induced mitogen-activated protein kinase (MAPK) pathways, as well as the phosphorylation of upstream c-raf and MEK1/2. In brief, kaempferol suppressed LPS-induced T helper 1 (Th1), T helper 2 (Th2), and neutrophil-related chemokines production in monocytes might be via the MAPK pathways.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Chemokine CCL22; Chemokines; Chemokines, CXC; Down-Regulation; Humans; Hypersensitivity; Interleukin-8; Kaempferols; Lipopolysaccharides; MAP Kinase Signaling System; Monocytes; Neutrophils; Osmolar Concentration; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein Isoforms; Protein Kinase Inhibitors; T-Lymphocytes, Helper-Inducer

Despite recent advances in understanding molecular mechanisms involved in glioblastoma progression, the prognosis of the most malignant brain tumor continues to be dismal. Because the flavonoid kaempferol is known to suppress growth of a number of human malignancies, we investigated the effect of kaempferol on human glioblastoma cells. Kaempferol induced apoptosis in glioma cells by elevating intracellular oxidative stress. Heightened oxidative stress was characterized by an increased generation of reactive oxygen species (ROS) accompanied by a decrease in oxidant-scavenging agents such as superoxide dismutase (SOD-1) and thioredoxin (TRX-1). Knockdown of SOD-1 and TRX-1 expression by small interfering RNA (siRNA) increased ROS generation and sensitivity of glioma cells to kaempferol-induced apoptosis. Signs of apoptosis included decreased expression of Bcl-2 and altered mitochondrial membrane potential with elevated active caspase-3 and cleaved poly(ADP-ribose) polymerase expression. Plasma membrane potential and membrane fluidity were altered in kaempferol-treated cells. Kaempferol suppressed the expression of proinflammatory cytokine interleukin-6 and chemokines interleukin-8, monocyte chemoattractant protein-1, and regulated on activation, normal T-cell expressed and secreted. Kaempferol inhibited glioma cell migration in a ROS-dependent manner. Importantly, kaempferol potentiated the toxic effect of chemotherapeutic agent doxorubicin by amplifying ROS toxicity and decreasing the efflux of doxorubicin. Because the toxic effect of both kaempferol and doxorubicin was amplified when used in combination, this study raises the possibility of combinatorial therapy whose basis constitutes enhancing redox perturbation as a strategy to kill glioma cells.

Topics: Apoptosis; Caspases; Cell Line, Tumor; Chemokine CCL2; Doxorubicin; Glioblastoma; Humans; Interleukin-6; Interleukin-8; Kaempferols; Membrane Potential, Mitochondrial; Mitochondria; Oxidants; Oxidative Stress; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; RNA, Small Interfering; Superoxide Dismutase; Superoxide Dismutase-1; Thioredoxins