interleukin-8 and Cholecystitis

We previously demonstrated that cancer-associated fibroblasts (CAFs) promoted the proliferation of gallbladder cancer (GBC) cells, but the mechanism is not clear. Neuropilin-1 (NRP-1) plays an important role in various malignancies as transmembrane glycoprotein. Our goal was to reveal the relationship between CAFs and NRP-1 and their potential functions in GBC. In this study, we found NRP-1 was overexpressed in GBC tissue, associated with poor survival and was up-regulated by CAFs. The cytokine array cluster analysis revealed IL-8 secreted by CAFs facilitated the up-regulation of NRP-1 in tumour cells. NRP-1 knockdown suppressed tumour growth in vivo. Gene expression microarray analysis showed 581 differentially regulated genes under NRP-1 knockdown conditions. Ingenuity pathway analysis demonstrated that NRP-1 knockdown may inhibit tumour progression by affecting cell proliferation. We then confirmed that NRP-1 knockdown in NOZ and GBC-SD cells significantly inhibited cell proliferation. Additionally, the IL-8 mediated MDM2 and CCNA2 expression were affected by NRP-1 knockdown. Our findings suggested that NRP-1 was up-regulated by CAF-secreted IL-8, which subsequently promoted GBC cell proliferation, and these molecules may serve as useful prognostic biomarkers and therapeutic targets for GBC.

Topics: Animals; Cancer-Associated Fibroblasts; Cell Line, Tumor; Cell Proliferation; Cholecystitis; Female; Gallbladder Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Male; Mice, Nude; Middle Aged; Multivariate Analysis; Neuropilin-1; Oligonucleotide Array Sequence Analysis; Prognosis; RNA, Small Interfering; Survival Analysis; Tumor Stem Cell Assay; Up-Regulation

To study whether H pylori are associated with chronic cholecystitis.. The subjects were divided into three groups: H pylori-infected cholecystitis group, H pylori-negative cholecystitis group and control group. Pathologic changes of the gallbladder were observed by optic and electronic microscopes and the levels of interleukin-1, 6 and 8 (IL-1, 6 and 8) were detected by radioimmunoassay.. Histological evidence of chronic cholecystitis including degeneration, necrosis, inflammatory cell infiltration, were found in the region where H pylori colonized. Levels of IL-1, 6 and 8 in gallbladder mucosa homogenates were significantly higher in H pylori-infected cholecystitis group than those in H pylori-negative cholecystitis group and control group.. H pylori infection may be related to cholecystitis.

Topics: Case-Control Studies; Cholecystitis; Chronic Disease; Gallbladder; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Metaplasia; Mucous Membrane

To investigate the effect of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and its ligand, ciglitazone, on inflammatory regulation of human gallbladder epithelial cells (HGBECs) and to assess the effect of human epithelial growth factor (hEGF) on growth of HGBECs.. HGBECs were cultured in media containing hEGF or hEGF-free media. HGBECs were divided into normal control group, inflammatory control group and ciglitazone group (test group). Inflammatory control group and ciglitazone group were treated with 5 microg/L of human interleukin-1beta (hIL-1beta) to make inflammatory model of HGBECs. The ciglitazone group was treated with various concentrations of ciglitazone, a potent ligand of PPAR-gamma. Subsequently, interleukin-8 (IL-8), IL-6, and tumor necrosis factor-alpha (TNF-alpha) concentrations in all groups were measured. The data were analyzed statistically.. HGBECs were cultured in medium successfully. The longevity of HGBECs in groups containing hEGF was longer than that in hEGF-free groups. So was the number of HGBECs. The longest survival time of HGBEC was 25 d. The inflammatory model of HGBECs was obtained by treating with hIL-1beta. The concentrations of IL-6 and IL-8 in ciglitazone group were lower than those in inflammatory control group (P<0.05). The secretion of IL-6 in inflammatory control group was higher (350.31+/-37.05 microg/L) than that in normal control group (50.0+/-0.00 microg/L, P<0.001). Compared to normal control group, IL-8 concentration in inflammatory control was higher (P<0.05).. hEGF improves the growth of HGBECs in vitro. Ciglitazone inhibits the inflammation of HGBECs in vitro and has potential therapeutic effect on cholecystitis in vivo.

Topics: Cells, Cultured; Cholecystitis; Epidermal Growth Factor; Epithelial Cells; Gallbladder; Humans; Inflammation; Interleukin-6; Interleukin-8; Ligands; Models, Biological; PPAR gamma; Thiazolidinediones; Tumor Necrosis Factor-alpha