interleukin-8 and caffeic-acid-phenethyl-ester

Salivary levels of interleukin-8 (IL-8) are elevated in patients with periodontitis. Caffeic acid phenethyl ester (CAPE) improves the periodontal status in subjects. However, whether CAPE can reduce IL-8 expression is unclear. We collected saliva to determine proinflammatory cytokine levels and used subgingival calculus and surrounding tissues from patients with periodontitis for oral microbiota analysis via 16s ribosomal RNA gene sequencing. THP-1 cells were stimulated with sterile-filtered saliva from patients, and target gene/protein expression was assessed. IL-8 mRNA expression was analyzed in saliva-stimulated THP-1 cells treated with CAPE and the heme oxygenase-1 (HO-1) inhibitor tin-protoporphyrin (SnPP). In 72 symptomatic individuals, IL-8 was correlated with periodontal inflammation (bleeding on probing,

Topics: Anti-Inflammatory Agents; Caffeic Acids; Cytokines; Heme Oxygenase-1; Humans; I-kappa B Proteins; Inflammation; Interleukin-8; Lipopolysaccharides; NF-kappa B; NF-KappaB Inhibitor alpha; Periodontitis; Phenylethyl Alcohol; Phosphorylation; Saliva; THP-1 Cells

Glaucoma is characterized by the death of retinal ganglion cells (RGCs) and visual field defects, and is a leading cause of blindness worldwide. Caffeic acid phenethyl ester (CAPE), a natural polyphenolic found in propolis from honeybee hives, can inhibit the activation of nuclear factor κ light‑chain‑enhancer of activated B cells (NF‑κB) and has therapeutic potential in inflammatory disease. The present study used a rat model of optic nerve crush (ONC) injury to investigate the effect of CAPE on glaucoma. The death of RGCs at day 14 was significantly reduced in CAPE‑treated animals compared with the non‑treated group according to Brn3a and TUNEL staining. In addition, CAPE decreased the severity of inflammation in the retina, reflected by the decreased expression of inflammatory cytokines, including interleukin (IL)‑8, IL‑6, inducible nitric oxide synthase, cycloooxygenase‑2, tumor necrosis factor‑α and chemokine C‑C ligand‑2, in CAPE‑treated rats. The hypertrophy of astrocytes and Müller cells (gliosis) caused by ONC was also found to be attenuated by CAPE, accompanied by the inhibition of NF‑κB signaling. Similarly, in vitro, CAPE suppressed the proliferation and migration of primary astrocytes induced by lipopolysaccharide, as well as the activation of NF‑κB. These results suggest that CAPE protected against RGC and attenuated inflammatory responses in a rat model of ONC by suppressing NF‑κB activation.

Topics: Animals; Astrocytes; Caffeic Acids; Cell Death; Cell Movement; Cell Nucleus; Cell Proliferation; Cell Survival; Chemokine CCL2; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Ependymoglial Cells; Glaucoma; Gliosis; In Situ Nick-End Labeling; Inflammation; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; NF-kappa B; Nitric Oxide Synthase Type II; Optic Nerve Injuries; Phenylethyl Alcohol; Rats; Rats, Sprague-Dawley; Retina; Retinal Ganglion Cells; Signal Transduction; Transcription Factor Brn-3A; Tumor Necrosis Factor-alpha

Chitinases are produced in significant quantities by hosts defending against infections with chitin-containing organisms. However, little is known about the immune response of exogenous chitinase in human epithelial cells. IL-8 has been suggested to have a role in the pathogenesis of the allergenic inflammation of bronchial asthma. We examined whether Streptomyces griseus (S. griseus) chitinase-induced IL-8 on airway epithelium and identified the involvement of intracellular signalling pathways. H292 cells were treated with S. griseus chitinase with different concentrations and times. The IL-8 levels were determined by specific human IL-8 enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction. Using a series of pharmacological inhibitors, we examined the upstream signalling pathway responsible for IL-8 expression in response to S. griseus chitinase. Cells exposed to S. griseus chitinase showed higher level of IL-8 protein production and mRNA expression. Cells stimulated by S. griseus chitinase resulted in the activation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK) and nuclear factor kappa-B (NF-kB) pathways. Inhibitors of Ca(2+)-dependent PKC (Ro-31-8220, calphostin C and Go6976) significantly abolished chitinase-induced expression of IL-8. However, Ca(2+)-independent PKC inhibitor (rottlerin) did not inhibit IL-8 expression. Through ERK inhibitor (U0126) and NF-kB inhibitor (caffeine acid phenethyl ester) treatment, it was proven that ERK and NF-kB regulated chitinase-induced IL-8 expression. We concluded that S. griseus chitinase-induced IL-8 expression was regulated by the activation of Ca(2+/-)-dependent PKC, ERK and NF-kB in human airway epithelial cells.

Topics: Blotting, Western; Butadienes; Caffeic Acids; Carbazoles; Cell Line, Tumor; Chitinases; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Extracellular Signal-Regulated MAP Kinases; Humans; Indoles; Interleukin-8; Naphthalenes; NF-kappa B; Nitriles; Phenylethyl Alcohol; Protein Kinase C; Protein Kinase Inhibitors; Respiratory Mucosa; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction

Nuclear factor-kappaB (NF-kappaB) plays a major role in host inflammatory responses and carcinogenesis and as such is an important drug target for adjuvant therapy. In this study, we examined the effect of caffeic acid phenethyl ester (CAPE), an NF-kappaB inhibitor, on Helicobacter pylori (H. pylori)-induced NF-kappaB activation in cell culture and chronic gastritis in Mongolian gerbils. In AGS gastric cancer cells, CAPE significantly inhibited H. pylori-stimulated NF-kappaB activation and mRNA expression of several inflammatory factors in a dose-dependent manner, and prevented degradation of IkappaB-alpha and phosphorylation of p65 subunit. To evaluate the effects of CAPE on H. pylori-induced gastritis, specific pathogen-free male, 6-week-old Mongolian gerbils were intragastrically inoculated with H. pylori, fed diets containing CAPE (0-0.1%) and sacrificed after 12 weeks. Infiltration of neutrophils and mononuclear cells and expression of NF-kappaB p50 subunit and phospho-IkappaB-alpha were significantly suppressed by 0.1% CAPE treatment in the antrum of H. pylori-infected gerbils. Labeling indices for 5'-bromo-2'-deoxyuridine both in the antrum and corpus and lengths of isolated pyloric glands were also markedly reduced at the highest dose, suggesting a preventive effect of CAPE on epithelial proliferation. Furthermore, in the pyloric mucosa, mRNA expression of inflammatory mediators including tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-2, IL-6, KC (IL-8 homologue), and inducible nitric oxide synthase was significantly reduced. These results suggest that CAPE has inhibitory effects on H. pylori-induced gastritis in Mongolian gerbils through the suppression of NF-kappaB activation, and may thus have potential for prevention and therapy of H. pylori-associated gastric disorders.

Topics: Animals; Blotting, Western; Caffeic Acids; Cytotoxins; Gastric Mucosa; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Immunoenzyme Techniques; Interferon-gamma; Interleukin-6; Interleukin-8; Male; NF-kappa B; Phenylethyl Alcohol; Phosphorylation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha

The results suggest that the anti-inflammatory effect of caffeic acid phenethyl ester (CAPE) is due to its inhibition of tumor necrosis factor (TNF)-alpha expression and interleukin (IL)-8 production. The anti-inflammatory effect of CAPE is possibly through the inhibition of nuclear factor (NF)-kappaB via the suppression of inhibitor-kappaB-alpha (IkappaB-alpha) degradation.. CAPE is a biologically active component of propolis, a resinous material obtained from bee hives, which originates from conifer bark. The effect of CAPE on lipopolysaccharide (LPS)-induced inflammatory reactions is not known. The aim of this study was to evaluate the anti-inflammatory effect of CAPE on cultured human middle ear epithelial cells (HMEECs).. The effect of CAPE on LPS-induced TNF-alpha expression was evaluated in HMEECs by real-time reverse transcription polymerase chain reaction (RT-PCR). LPS-induced IL-8 production was determined by enzyme-linked immunosorbent assay (ELISA), and LPS-induced IkappaB-alpha degradation was followed by Western blot analysis.. CAPE significantly inhibited LPS-induced up-regulation of TNF-alpha in a dose-dependent manner. IL-8 production by LPS was significantly suppressed by the CAPE pretreatment. Furthermore, LPS-induced IkappaB-alpha degradation was suppressed by the CAPE pretreatment.

Topics: Caffeic Acids; Cell Line; Gene Expression; Humans; Inflammation Mediators; Interleukin-8; Lipopolysaccharides; NF-kappa B; Otitis Media; Phenylethyl Alcohol; Tumor Necrosis Factor-alpha

Carrageenan is a high molecular weight sulfated polygalactan used to improve the texture of commercial food products. Its use increased markedly during the last half century, although carrageenan is known to induce inflammation in rheumatological models and in intestinal models of colitis. We performed studies to determine its direct effects on human intestinal cells, including normal human intestinal epithelial cells from colonic surgeries, the normal intestinal epithelial cell line NCM460, and normal rat ileal epithelial cells. Cells were treated with high molecular weight lambda-carrageenan at a concentration of 1 mug/ml for 1-96 h. IL-8, IL-8 promoter activity, total and nuclear NF-kappaB, IkappaBalpha, phospho-IkappaBalpha, and Bcl10 were assessed by immunohistochemistry, Western blot, ELISA, and cDNA microarray. Increased Bcl10, nuclear and cytoplasmic NF-kappaB, IL-8 promoter activation, and IL-8 secretion were detected following carrageenan exposure. Knockdown of Bcl10 by siRNA markedly reduced the increase in IL-8 that followed carrageenan exposure in the NCM460 cells. These results show, for the first time, that exposure of human intestinal epithelial cells to carrageenan triggers a distinct inflammatory pathway via activation of Bcl10 with NF-kappaB activation and upregulation of IL-8 secretion. Since Bcl10 contains a caspase-recruitment domain, similar to that found in NOD2/CARD15 and associated with genetic predisposition to Crohn's disease, the study findings may represent a link between genetic and environmental etiologies of inflammatory bowel disease. Because of the high use of carrageenan as a food additive in the diet, the findings may have clinical significance.

Topics: Adaptor Proteins, Signal Transducing; Animals; B-Cell CLL-Lymphoma 10 Protein; Caffeic Acids; Carrageenan; Cell Line; Cells, Cultured; Epithelial Cells; Gene Expression Regulation; Humans; I-kappa B Proteins; Interleukin-8; Intestinal Mucosa; Models, Biological; NF-kappa B; NF-KappaB Inhibitor alpha; Phenylethyl Alcohol; Phosphorylation; Promoter Regions, Genetic; Rats; RNA, Small Interfering; Signal Transduction; Transfection

The pathologic changes within the intestinal muscle layer may be at the origin of the cytokines that account for acute radiation-induced inflammation. We were specifically interested in evaluating the efficacy of an inhibitor of nuclear transcription factor kappa B (NF-kappaB) activation that is involved in regulating cytokine expression.. Cytokine expression was analyzed in the ileal muscularis layer by reverse transcriptase-polymerase chain reaction (RT-PCR) at 3 h, 6 h, and 3 days after a 10-Gy gamma whole-body irradiation of rats. Caffeic acid phenethyl ester (CAPE) was injected intraperitoneally (30 mg/kg) 15 min before irradiation and once a day for 3 days.. Interleukin (IL)-1beta, tumor necrosis factor alpha (TNF-alpha), and IL-6 mRNA increased at 3 h and 6 h after irradiation, and expression of IL-6 and IL-8 was elevated at 3 days. On the other hand, levels of the anti-inflammatory cytokine IL-10 were markedly lower on Day 3. Overexpression of IL-6 on Day 3 was combined with upregulation of the IL-6 receptors (gp130/gp80) and suppressor of cytokine signaling-3 (SOCS3) genes. CAPE treatment did not significantly change IL-1beta or TNF-alpha expressions in the irradiated rats; it increased IL-10 expression at 6 h but had no effect on it on Day 3. CAPE treatment inhibited the radiation-induced expression of IL-6, IL-6 receptors (IL-6rs), and SOCS3 at 3 days.. In vivo, irradiation induced a cascade of inflammatory responses that involved the transcription factor NF-kappaB; this inflammation was reduced by CAPE treatment.

Topics: Animals; Caffeic Acids; Enteritis; Gamma Rays; Ileum; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Interleukins; Male; Muscle, Smooth; NF-kappa B; Phenylethyl Alcohol; Radiation Injuries; Rats; Rats, Wistar; Receptors, Interleukin-6; Repressor Proteins; Reverse Transcriptase Polymerase Chain Reaction; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Time Factors; Transcription Factors; Tumor Necrosis Factor-alpha; Whole-Body Irradiation

Endothelial and monocytic cells appear to play a key role in the initiation and progression of atherosclerosis and restenosis via the upregulation of inflammatory cytokines and the formation of oxidized low-density lipoprotein (ox-LDL). However, the role of smooth muscle cells (SMCs) has been underestimated and is not well understood. It was investigated for the first time that native LDL stimulates human SMCs to secrete IL-8. The aim of this study was to investigate the signaling pathway involved in the upregulation of IL-8, induced by LDL in human aortic SMCs.. LDL-induced IL-8 expression (mRNA and protein) is specific to SMCs and likely to be regulated at the transcription level in dose- and time-dependent manners, as judged by experiments with actinomycin D and ELISA. Although both p38 and ERK 1/2 MAPKs were activated by LDL, only p38 MAPK is responsible for the LDL effects, as evidenced by a complete blockade of IL-8 upregulation by SB203580. Pretreatment with catalase significantly decreased the extent of IL-8 upregulation, indicating that H2O2 is necessary for the LDL response. Activation of activator protein (AP)-1, but not nuclear factor (NF)-kappaB, by p38 or H2O2 appears to be necessary along with the concomitant upregulation of c-fos and c-JUN, as judged by electrophoretic mobility shift and luciferase reporter assays.. These data demonstrated that LDL stimulates SMCs to induce IL-8 production in dose- and time-dependent manners at the transcription level and that the LDL signaling in hAoSMCs is conveyed via the generation of H2O2, the phosphorylation of p38 MAPK, the activation of AP-1, and the participation of NF-kappaB.

Topics: Aorta; Caffeic Acids; Cells, Cultured; Coronary Vessels; Dactinomycin; Dose-Response Relationship, Drug; Flavonoids; Humans; Hydrogen Peroxide; Imidazoles; Interleukin-8; Lipoproteins, LDL; Mitogen-Activated Protein Kinases; Muscle, Smooth, Vascular; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phenylethyl Alcohol; Pyridines; Sesquiterpenes; Time Factors; Transcription Factor AP-1; Tumor Necrosis Factor-alpha