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IL-8 Response (il-8 + response)
Selected AbstractsCharacterization of epithelial IL-8 response to inflammatory bowel disease mucosal E. coli and its inhibition by mesalamine,INFLAMMATORY BOWEL DISEASES, Issue 2 2008Sreedhar Subramanian MD Abstract Background: Mucosally adherent E. coli are found in inflammatory bowel disease (IBD) and colon cancer. They promote release of the proinflammatory cytokine interleukin-8 (IL-8). We explored mechanisms for this release and its inhibition by drugs. Methods: IL-8 release from colon epithelial cells in response to mucosal E. coli isolates from IBD, colon cancer, and controls was characterized at the cellular and molecular level. Results: IL-8 response of HT29 cells was greater with Crohn's disease (689 ± 298 [mean ± SD] pg IL-8/mL at 4 hours, n = 7) and colon cancer isolates (532 ± 415 pg/mL, n = 14) than with ulcerative colitis (236 ± 58 pg/mL, n = 6) or control isolates (236 ± 100 pg/mL, n = 6, P < 0.0001). Bacterial supernatants contained shed flagellin that triggered IL-8 release. For whole bacteria the IL-8 response to E. coli that agglutinate red blood cells (548 ± 428 pg IL-8/mL, n = 16), a function that correlates with epithelial invasion, was greater than for nonhemagglutinators (281 ± 253 pg/mL, n = 17; P < 0.0001). This was particularly marked among E. coli that, although flagellate, could not release IL-8 from TLR5-transfected HEK293 cells. IL-8 release was mediated by extracellular-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) and inhibited by mesalamine, but not hydrocortisone, at therapeutic concentrations. Conclusions: Mucosa-associated E. coli shed flagellin that elicits epithelial IL-8 release but this may only become relevant when the mucosal barrier is weakened to expose basolateral TLR5. Adherent and invasive IBD and colon cancer E. coli isolates also elicit a flagellin-independent IL-8 response that may be relevant when the mucosal barrier is intact. The IL-8 release is MAPK-dependent and inhibited by mesalamine. (Inflamm Bowel Dis 2007) [source] Contrasting responses of human gingival and periodontal ligament fibroblasts to bacterial cell-surface components through the CD14/Toll-like receptor systemMOLECULAR ORAL MICROBIOLOGY, Issue 1 2003J. Hatakeyama We compared human periodontal ligament fibroblasts with human gingival fibroblasts isolated from the same donor to examine interleukin-8 (IL-8) responses of the cells to Salmonella lipopolysaccharide, a water-soluble peptidoglycan from Staphylococcus epidermidis and the synthetic muramyldipeptide, with special reference to the possible involvement of the CD14/Toll-like receptor (TLR) system of the cells in the responses. Human gingival fibroblasts expressed CD14 on their surfaces and strongly expressed CD14 mRNA, while human periodontal ligament fibroblasts showed considerably lower levels of expression in both respects. Both cells expressed mRNA of TLR-related molecules, i.e. TLR2, TLR4, MD-2 and MyD88, although human periodontal ligament fibroblasts expressed TLR2 more strongly than human gingival fibroblasts. Human gingival fibroblasts exhibited a stronger IL-8 response than human periodontal ligament fibroblasts to lipopolysaccharide, while human periodontal ligament fibroblasts exhibited a response comparable to, or slightly stronger than, that of human gingival fibroblasts to S. epidermidis peptidoglycan and muramyldipeptide. The IL-8 responses of both cells to lipopolysaccharide and S. epidermidis peptidoglycan were completely inhibited by antihuman CD14 monoclonal antibody (MAb). The responses of both cells to lipopolysaccaride were significantly inhibited by antihuman TLR4 MAb, while those to S. epidermidis peptidoglycan were inhibited by antihuman TLR2 MAb. In contrast, muramyldipeptide activated both types of cells in a TLR2- and TLR4-independent manner, although the activities of muramyldipeptide on human gingival fibroblasts, but not human periodontal ligament fibroblasts, were significantly inhibited by anti-CD14 MAb. [source] Influence of antiseptic agents on interleukin 8 release and transmigration of polymorphonuclear granulocytes in an in vitro model of peritonitisBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2000W. Sendt Background The effect of antiseptic agents on peritoneal cells is ill defined. The influence of taurolidine (TAU) and polyhexamide (HEX) was investigated in an in vitro model. Methods Human umbilical vein endothelial cells (HUVECs) and human peritoneal mesothelial cells (HPMCs) were laid on collagen-coated filter inserts (HUVECs on the bottom, HPMCs on the top), thus representing a two-chamber peritoneal model. When confluence was reached, HPMCs were stimulated with 0·5 ml tumour necrosis factor (TNF) , 10 ,g ml,1 for 4 h. Afterwards 0·5 ml TAU (1 and 2 per cent) or 0·5 ml HEX (0·1 and 0·2 per cent) solutions were added to the upper compartment. After 1 h polymorphonuclear granulocytes (PMNs) (105 ml,1) were added to the lower compartment. After 2 and 6 h aliquots were taken from both compartments, transmigrated PMNs were counted and interleukin (IL) 8 concentrations were measured. Controls were either TNF-,-stimulated HPMCs or stimulated HPMCs where culture medium had been substituted for TNF-,. Significance of differences was assessed by analysis of variance with Bonferroni corrections. Correlations were calculated by linear regression analysis. Results Stimulation with TNF-, led to a time-dependent increase in PMN transmigration. IL-8 secretion into the apical compartment increased time dependently, resulting in a gradient between the two chambers. After substitution of the stimulus by culture medium, significantly less IL-8 was measured in both compartments. PMN transmigration was almost absent. Addition of HEX resulted in an initial increase in IL-8 levels comparable to TNF controls without further changes. A concentration-dependent decrease in IL-8 gradient was associated with reduced transmigration. The IL-8 gradient between the upper and lower chambers correlated significantly with PMN transmigration (r = 0·8205, P < 0·0001). Conclusion The decrease in IL-8 gradients by HEX and the diminished IL-8 response after addition of TAU may reflect either anti-inflammatory effects or cellular damage. Both antiseptic solutions reduced PMN migration, irrespective of continuous stimulation in this model. © 2000 British Journal of Surgery Society Ltd [source] Role of EHEC O157:H7 virulence factors in the activation of intestinal epithelial cell NF-,B and MAP kinase pathways and the upregulated expression of interleukin 8CELLULAR MICROBIOLOGY, Issue 10 2002M. Cecilia Berin Summary Enterohaemorrhagic Escherichia coli O157:H7 (EHEC) is a gastrointestinal pathogen that is generally non-invasive for intestinal epithelial cells, yet causes acute intestinal inflammation, diarrhoea, haemorrhagic colitis and haemolytic uraemic syndrome. To study signal transduction pathways activated in human intestinal epithelial cells by EHEC, we took advantage of EHEC O157:H7 and isogenic mutants deficient in the major EHEC virulence factors, intimin (eae,) and Shiga toxin (stx,). Infection with wild-type EHEC activated p38 and ERK MAP kinases and the nuclear translocation of the transcription factor NF-,B. Downstream, this was accompanied by increased expression of mRNA and protein for the neutrophil chemoattractant IL-8. Isogenic eae, and stx, mutants also activated p38 and ERK MAP kinases, and NF-,B and stimulated increases in IL-8 protein secretion similar to those of wild-type EHEC. Further, inhibition of either p38, ERK or NF-,B activation abrogated the IL-8 response induced by wild-type EHEC and the mutants. Epithelial cell MAP kinase and NF-,B pathways leading to IL-8 secretion were also activated by isolated EHEC H7 flagellin, which was active when added to either the apical or basolateral surface of polarized human intestinal epithelial cells. We conclude that EHEC interacting with intestinal epithelial cells activates intracellular signalling pathways and an epithelial cell proinflammatory response independent of either Shiga toxin or intimin, two of the major known virulence factors of EHEC. The activation of proinflammatory signals in human colon epithelial cells in response to this non-invasive pathogen appears to depend to a significant extent on H7 flagellin. [source] |