interleukin-8 and naringenin

This study aimed to investigate how naringenin (Nar) affected the anti-inflammatory, vascula-rization, and osteogenesis differentiation of human periodontal ligament stem cells (hPDLSCs) stimulated by lipopolysaccharide (LPS) and to preliminarily explore the underlying mechanism.. Cell-counting kit-8 (CCK8), cell scratch test, and Transwell assay were used to investigate the proliferation and migratory capabilities of hPDLSCs. Alkaline phosphatase (ALP) staining, alizarin red staining, lumen-formation assay, enzyme-linked immunosorbent assay, quantitative timed polymerase chain reaction, and Western blot were used to measure the expression of osteopontin (OPN), Runt-related transcription factor 2 (RUNX2), vascular endothlial growth factor (VEGF), basic fibroblast growth factor (bFGF), von Willebrand factor (vWF), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6.. We observed that 10 μmol/L Nar could attenuate the inflammatory response of hPDLSCs stimulated by 10 μg/mL LPS and promoted their proliferation, migration, and vascularization differentiation. Furthermore, 0.1 μmol/L Nar could effectively restore the osteogenic differentiation of inflammatory hPDLSCs. The effects of Nar's anti-inflammatory and promotion of osteogenic differentiation significantly decreased and inflammatory vascularization differentiation increased after adding AMD3100 (a specific CXCR4 inhibitor).. Nar demonstrated the ability to promote the anti-inflammatory, vascularization, and osteogenic effects of hPDLSCs stimulated by LPS, and the ability was associated with the stromal cell-derived factor/C-X-C motif chemokine receptor 4 signaling axis.

Topics: Anti-Inflammatory Agents; Cell Differentiation; Cell Proliferation; Cells, Cultured; Chemokine CXCL12; Humans; Interleukin-8; Lipopolysaccharides; Osteogenesis; Periodontal Ligament; Receptors, Chemokine; Stem Cells

Systemic inflammation, circulating immune cell activation, and endothelial cell damage play a critical role in vascular pathogenesis. Flavonoids have shown anti-inflammatory effects. In this study, we investigated the effects of different flavonoids on the production of pro-inflammatory interleukin (IL) 1β, 6, and 8, and tumor necrosis factor α (TNF-α), in peripheral blood cells. Methods: We studied the whole blood from 36 healthy donors. Lipopolysaccharide (LPS)-stimulated (0.5 μg/mL) whole-blood aliquots were incubated in the presence or absence of different concentrations of quercetin, rutin, naringenin, naringin, diosmetin, and diosmin for 6 h. Cultures were centrifuged and the supernatant was collected in order to measure IL-1β, TNF-α, IL-6, and IL-8 production using specific immunoassay techniques. This production was significantly inhibited by quercetin, naringenin, naringin, and diosmetin, but in no case by rutin or diosmin. Flavonoids exert different effects, maybe due to the differences between aglycons and glucosides present in their chemical structures. However, these studies suggest that quercetin, naringenin, naringin, and diosmetin could have a potential therapeutic effect in the inflammatory process of cardiovascular disease.

Topics: Anti-Inflammatory Agents; Diosmin; Dose-Response Relationship, Immunologic; Female; Flavanones; Flavones; Flavonoids; Flavonols; Healthy Volunteers; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Lipopolysaccharides; Male; Primary Cell Culture; Quercetin; Rutin; Tumor Necrosis Factor-alpha; Young Adult

Naringenin is found mainly in citrus fruits, and is thought to be beneficial in the prevention and control of lung diseases. This study aims to investigate the mechanisms of naringenin against the damage in the lung caused by cigarette smoke. A system bioinformatic approach was proposed to predict the mechanisms of naringenin for protecting lung health. Then, we validated this prediction in BEAS-2B cells treated with cigarette smoke extract (CSE). System bioinformatic analysis indicated that naringenin exhibits protective effects on lung through the inhibition of inflammation and suppression of oxidative stress based on a multi-pathways network, mainly including oxidative stress pathway, Nrf2 pathway, Lung fibrosis pathway, IL-3 signaling pathway, and Aryl hydrocarbon receptor pathway. The in vitro results showed that naringenin significantly attenuated CSE-induced up-regulation of IL-8 and TNF-α. CSE stimulation increased the mRNA expressions of Nrf2, HO-1, and NQO1; the levels of total protein and nuclear protein of Nrf2; and the activity of SOD on days 2 and 4; but decreased these indexes on day 6. Naringenin can balance the antioxidant system by regulating Nrf2 and its downstream genes, preliminarily validating that Nrf2 pathway is involved in the protection offered by naringenin against cigarette smoke-induced damage to the lung. It suggests that dietary naringenin shows possible potential use in the management of lung health.

Topics: Cell Line; Cell Survival; Cigarette Smoking; Computational Biology; Epithelial Cells; Flavanones; Gene Expression Regulation; Gene Ontology; Heme Oxygenase-1; Humans; Interleukin-8; Lung; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Protein Interaction Maps; Superoxide Dismutase; Tumor Necrosis Factor-alpha

A tenet of contemporary obstetrics is that a significant proportion of preterm births involve bacterial infection. Bacterial endotoxin induces pro-inflammatory cytokines, prostaglandins and proteases via the pro-inflammatory pathway nuclear factor-κB (NF-κB), which plays a key role in initiating uterine contractions and rupture of foetal membranes. In non-gestational tissues, the phytophenols curcumin, naringenin and apigenin exert anti-inflammatory properties via inhibition of NF-κB. The aim of this study was to determine whether these treatments regulate pro-inflammatory and pro-labour mediators in human gestational tissues. Placenta, foetal membranes and myometrium were treated with curcumin, naringenin and apigenin in the presence of lipopolysaccharide (LPS) or interleukin (IL)-1β. In placenta and foetal membranes, all treatments significantly reduced LPS-stimulated release and gene expression of pro-inflammatory cytokines IL-6 and IL-8; placenta decreased cyclooxygenase (COX-2) mRNA expression, subsequent release of prostaglandins PGE2 and PGF2α and expression and activity of matrix-degrading enzyme matrix metalloproteinase (MMP)-9. In myometrial cells, all treatments attenuated IL-1β-induced COX-2 expression, release of PGE2 and PGF2α and expression and activity of MMP-9. Although naringenin significantly attenuated IL-1β-induced IL-6 and IL-8 mRNA expression and release, there was no effect of curcumin and apigenin. LPS-stimulated release of 8-isoprostane, a marker of oxidative stress, was attenuated by all treatments. NF-κB p65 DNA-binding activity was also decreased using these treatments. In conclusion, curcumin, naringenin and apigenin exert anti-inflammatory properties in human gestational tissues by inhibiting the transcriptional activity of NF-κB. Further studies should be undertaken to define a possible implication of these natural spices in the management of preterm labour and delivery.

Topics: Apigenin; Cells, Cultured; Curcumin; Cyclooxygenase 2; Dietary Supplements; Extraembryonic Membranes; Female; Flavanones; Humans; In Vitro Techniques; Inflammation; Interleukin-6; Interleukin-8; Myometrium; Placenta; Pregnancy; Premature Birth; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factor RelA

Chronic inflammation, a process linked to increased oxidative stress, may induce many diseases. Whether beta-carotene prevents inflammation is unclear. Using phorbol-12-myristate-13-acetate (PMA)-stimulated HL-60 cells, we investigated the effects of 2 or 20 microM beta-carotene on the inflammatory reaction of monocyte/macrophage-like cells and the modulation of 20 microM quercetin or naringenin, two flavonoids, of the effects of beta-carotene. The effects of quercetin and naringenin were compared with that of alpha-tocopherol, a well-known antioxidant. The stimulated HL-60 cells were also co-incubated with A549 cells to investigate the DNA-damaging ability of the stimulated monocyte/macrophage-like cells on target cells. Our results showed that preincubation with 20 microM beta-carotene significantly enhanced the release of two pro-inflammatory mediators, interleukin-8 and tumor necrosis factor-alpha, in PMA-stimulated HL-60 cells and slightly increased the DNA-damaging ability of these cells. By contrast, 2 microM beta-carotene had an inhibitory effect on the inflammatory reaction in PMA-stimulated cells. The higher dose of beta-carotene also exerted pro-inflammatory effects in lipopolysaccharide-stimulated RAW264.7 cells. Furthermore, quercetin, naringenin, and alpha-tocopherol partly suppressed the pro-inflammatory effects of 20 microM beta-carotene on PMA-stimulated HL-60 cells, and the suppressing effects of quercetin and naringenin were better than or similar to those of alpha-tocopherol. Quercetin also additively or synergistically enhanced the inhibitory effects of 2 microM beta-carotene on the secretion of pro-inflammatory mediators and the DNA-damaging ability of PMA-stimulated HL-60 cells. The mechanisms underlying the effect of the flavonoids were associated with their antioxidant activity and inhibition of the production of pro-inflammatory cytokines. Our results urge consideration of the safety of beta-carotene supplementation concerning effects on inflammation and suggest that the interaction between beta-carotene and quercetin or naringenin may alter the effects of beta-carotene on the secretion of pro-inflammatory mediators.

Topics: alpha-Tocopherol; Animals; beta Carotene; Cell Differentiation; Cells, Cultured; DNA Damage; Dose-Response Relationship, Drug; Flavanones; HL-60 Cells; Humans; Interleukin-8; Lipopolysaccharides; Mice; Quercetin; Reactive Oxygen Species; Tetradecanoylphorbol Acetate; Thiobarbituric Acid Reactive Substances; Time Factors; Tumor Necrosis Factor-alpha

Periodontitis is a chronic inflammatory disease of bacterial etiology, affecting tooth-supporting tissues. The host inflammatory response to periodontopathogens, notably the high and continuous production of cytokines, is considered a major factor causing the local tissue destruction observed in periodontitis. The aim of the present study was to investigate the effect of naringenin, a major flavanone in grapefruits and tomatoes, on the lipopolysaccharide-induced pro-inflammatory cytokine production by host cells, using two different models.. The effect of naringenin was characterized using macrophages stimulated with the lipopolysaccharide of either Aggregatibacter actinomycetemcomitans or Escherichia coli and using whole blood stimulated with A. actinomycetemcomitans lipopolysaccharide, in the presence or absence of naringenin. Lipopolysaccharide-induced interleukin-1 beta, interleukin-6, interleukin-8 and tumor necrosis factor-alpha production by macrophages and whole-blood samples treated with naringenin were evaluated using an enzyme-linked immunosorbent assay. Changes in the phosphorylation states of macrophage kinases induced by A. actinomycetemcomitans lipopolysaccharide and naringenin were characterized by immunoblot screening.. Our results clearly indicated that naringenin is a potent inhibitor of the pro-inflammatory cytokine response induced by lipopolysaccharide in both macrophages and in whole blood. Naringenin markedly inhibited the phosphorylation on serines 63 and 73 of Jun proto-oncogene-encoded AP-1 transcription factor in lipopolysaccharide-stimulated macrophages.. The results from the present study suggest that naringenin holds promise as a therapeutic agent for treating inflammatory diseases such as periodontitis.

Topics: Aggregatibacter actinomycetemcomitans; Anti-Inflammatory Agents; Escherichia coli; Flavanones; Humans; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Interleukin-8; Lipopolysaccharides; Macrophages; p38 Mitogen-Activated Protein Kinases; Periodontitis; Phosphorylation; Phosphotransferases; Protein Serine-Threonine Kinases; Proto-Oncogene Mas; Proto-Oncogene Proteins c-jun; Serine; Transcription Factor AP-1; Tumor Necrosis Factor-alpha; U937 Cells