Inhibition Of Interleukin-8 Release Research Articles

Inhibition of interleukin-8 release in human neutrophils by Melodorum fruticosum

Inhibition of interleukin-8 release in human neutrophils by Melodorum fruticosum

The inhibitory effect of flavonoids on interleukin-8 release by human gastric adenocarcinoma (AGS) cells infected with cag PAI (+) Helicobacter pylori.

IntroductionIt is well known that the presence of Helicobacter pylori in the stomach induces gastritis and causes an immune response. Exposure of gastric epithelial cell lines to this germ induces the secretion of interleukin-8 (IL-8), which is a potent PMN-activating chemotactic cytokine. Interleukin-8 is usually elevated in gastric biopsy samples of patients with H. pylori-associated gastritis and significantly increases in the supernatant of in vitro cultivated biopsy samples of gastric mucosa with active H. pylori gastritis. Interleukin-8 is an activating factor for leucocytes and other pro-inflammatory factors, free radicals, and proteolytic enzymes. That is why natural compounds potentially useful in therapy are still investigated – among them flavonoids. They reveal anti-oxidative and anti-inflammatory activities and significantly inhibit the gastric mucosa damage.The aim of the studyWas the estimation of the anti-inflammatory effects of flavonoids on H. pylori-induced activation of human gastric adenocarcinoma cells (AGS). After infection of AGS cells by cag PAI (+) H. pylori in vitro, secretion of IL-8, effects of flavonoids on viability of AGS cells, and effects of flavonoids on increase of H. pylori were determined. Such flavones as chrysin, quercetin, kaemferide, flavanone, galangin, and kaempferol were examined.ResultsThis study has shown an inhibitory effect of flavonoids on the release of IL-8 through infected AGS cells (except chrysin), and no toxic effects to AGS cells were observed. Galangin revealed antibacterial effects against H. pylori. Flavonoids limit the inflammatory process through the inhibition of IL-8 release in infected AGS cells with H. pylori. The strongest inhibitor of IL-8 was galangin.

Probiotic Screening and Safety Evaluation of Lactobacillus Strains from Plants, Artisanal Goat Cheese, Human Stools, and Breast Milk

The aim of this study was to select autochthonous strains of Lactobacillus from stools of healthy infants and adults, human milk, artisanal goat cheese, and fruits and vegetables according to their probiotic properties and safety. From 421 strains of Lactobacillus isolated, 102 (24.2%) were shown to be tolerant to gastric pH and bile salts; they were used to determine their anti-Helicobacter pylori (agar diffusion assay), antioxidant (oxygen radical absorption capacity), and anti-inflammatory (inhibition of interleukin-8 release by tumor necrosis factor-α-stimulated HT-29 cells) activities as well as their ability to adhere to intestinal (Caco-2) and gastric (AGS) epithelial cells. Results obtained were compared with three commercial probiotic Lactobacillus rhamnosus GG, L. plantarum 299v, and L. johnsonii NCC533. The five strains most efficient according to these activities were subsequently identified by sequencing their 16S rRNA gene, their susceptibility to antibiotics was determined, and their safety evaluated in mice. One strain of L. plantarum was discarded due to the higher prevalence of liver bacterial translocation observed in the animals fed this strain. In conclusion, four autochthonous strains of L. rhamnosus were finally selected with probiotic properties and safety allowing their eventual use in human studies. These results contribute to increase the diversity of probiotic strains available for the development of nutraceuticals and functional foods.

Inhibition of interleukin-8 release in the human colonic epithelial cell line HT-29 by cannabinoids

We have investigated the effects of cannabinoid agonists and antagonists on tumour necrosis factor-α (TNF-α)-induced secretion of interleukin-8 from the colonic epithelial cell line, HT-29. The cannabinoid receptor agonists {(−)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)-phenyl]4-[3-hydroxypropyl]cyclo-hexan-1-ol} (CP55,940); Δ-9-tetrahydrocannabinol; [ R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl) methyl] pyrrolo[1,2,3-de]1,4-benzoxazin-6-yl](1-naphthyl) methanone mesylate} (WIN55,212-2) and 1-propyl-2-methyl-3-naphthoyl-indole (JWH 015) inhibited TNF-α induced release of interleukin-8 in a concentration-dependent manner. The less active enantiomer of WIN55212-2, [ S(−)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]1,4-benzoxazin-6-yl](1-naphthyl) methanone mesylate (WIN55212-3), and the cannabinoid CB 1 receptor agonist arachidonoyl-2-chloroethylamide (ACEA) had no significant effect on TNF-α-induced release of interleukin-8. The cannabinoid CB 1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1,4-pyrazole-3-carboxamide hydrochloride (SR141716A; 10 −6 M) antagonised the inhibitory effect of CP55,940 (pA 2=8.3±0.2, n=6) but did not antagonise the inhibitory effects of WIN55212-2 and JWH 015. The cannabinoid CB 2 receptor antagonist N-(1,S)-endo1,3,3-trimethylbicyclo(2,2,1)heptan-2-yl)-5(4-chloro-3-methyl-phenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; 10 −6 M) antagonised the inhibitory effects of CP55,940 (pA 2=8.2±0.8, n=6), WIN55212-2 (pA 2=7.1±0.3, n=6) and JWH 015 (pA 2=7.6±0.3, n=6) , respectively. Western immunoblotting of HT-29 cell lysates revealed a protein with a size that is consistent with the presence of cannabinoid CB 2 receptors. We conclude that in HT-29 cells, TNF-α-induced interleukin-8 release is inhibited by cannabinoids through activation of cannabinoid CB 2 receptors.

Role of haemolytic and non-haemolytic phospholipase C from Pseudomonas aeruginosa in interleukin-8 release from human monocytes.

A massive accumulation of neutrophils, mainly due to enhanced interleukin-8 (IL-8) levels, is believed to contribute to the deleterious effects of Pseudomonas aeruginosa lung infection, e.g., in cystic fibrosis (CF). Antibodies to phospholipase C, an exoenzyme of P. aeruginosa, are detected early and at high levels in CF patients. However, P. aeruginosa produces at least two types of phospholipase C (PLC), one haemolytic (PLC-H) and the other non-haemolytic (PLC-N), both with mol.wts of c. 77 kDa. Experiments were performed to evaluate the potential contribution of P. aeruginosa PLC to neutrophil accumulation during infection. Therefore, P. aeruginosa PLC-H and PLC-N were compared with regard to IL-8 generation from human monocytes. Purified PLC-H as well as culture supernates (mol.wt > 50 kDa) of a P. aeruginosa strain capable of producing both PLC-H and PLC-N, and mutant strains deficient in the production of one or other phospholipase, or both, were examined. Purified PLC-H (only at low concentrations up to 1 unit/4 x 10(5) monocytes), induced a dose-dependent increase in IL-8 release and IL-8-specific mRNA expression over that of unstimulated cells (at 4-, 12- and 24-h incubation times). Higher concentrations of PLC-H led to a decrease in IL-8 release and IL-8-specific mRNA expression. These findings were confirmed by the results obtained with the supernates of cultures of mutant strains of P. aeruginosa PAO1 that produced either a PLC-H or PLC-N or neither. Stimulation and inhibition of IL-8 release and mRNA expression were associated with a culture supernate fraction of mol. wt > 50 kDa and containing PLC-H. These results contribute to the understanding of the role of both P. aeruginosa PLC in IL-8 generation during their interaction with human monocytes.