interleukin-8 and Colonic-Diseases

We evaluated the diagnostic performance of a newly-launched magnetic bead-based multiplex immunoassay panel including cancer, apoptotic, immunological and angiogenesis biomarkers for differential diagnosis of colorectal cancer (CRC).. Serum samples of 106 individuals comprising of 35 patients with CRC (23 colon cancer, 12 rectal cancer), 20 with respective benign colorectal diseases and 51 healthy controls were analyzed by the Milliplex™ MAP Human Circulating Cancer Biomarker Panel 1 run on the Bio-Plex™ 200 System.. IL-8, CEA, HGF, TNFα, CYFRA 21-1, OPN, TGFα, CA 19-9, CA 125, AFP and sFas showed significantly higher levels in cancer samples compared to healthy controls. It is noteworthy that comparing CRC and benign colorectal disease samples, many immunological and cell death markers were elevated as well. Exclusively, six markers were distinguished significantly between both groups: CEA showed the best performance in differential diagnosis reaching an AUC of 0.859 in ROC curve followed by CA 19-9, CYFRA 21-1, IL-8, CA 125 and OPN reaching AUCs between 0.696 and 0.744. Correlation with tumor stage was found for CEA, sFas and CYFRA 21-1. Finally marker scores were assembled showing that a combination of CEA and CA 19-9 had a higher AUC (0.893) compared to the biomarkers alone.. Differential diagnosis of CRC can be improved by new biomarker classes and their combination assessed by novel multiplex immunoassay.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Carcinoembryonic Antigen; Colonic Diseases; Diagnosis, Differential; Female; Humans; Immunoassay; Interleukin-8; Keratin-19; Male; Middle Aged; Neoplasm Staging; Osteopontin; Rectal Diseases; Young Adult

Topics: Aged; Colonic Diseases; Cytokines; Dysentery, Amebic; Gene Expression; Humans; Interleukin-1; Interleukin-8; Intestinal Mucosa; Male; Oncogenes; Reverse Transcriptase Polymerase Chain Reaction

We sought to determine if infection of the colon with Entamoeba histolytica induces the expression of cyclooxygenase-2 and, if it does, to determine the contribution of prostaglandins produced through cyclooxygenase-2 to the host response to amebic infection. Human fetal intestinal xenografts were implanted subcutaneously in mice with severe combined immunodeficiency and allowed to grow; the xenografts were then infected with E. histolytica trophozoites. Infection with E. histolytica resulted in the expression of cyclooxygenase-2 in epithelial cells and lamina propria macrophages. Infection with E. histolytica increased prostaglandin E(2) (PGE2) levels 10-fold in the xenografts and resulted in neutrophil infiltration, as manifested by an 18-fold increase in myeloperoxidase activity. Amebic infection also induced an 18-fold increase in interleukin 8 (IL-8) production and a >100-fold increase in epithelial permeability. Treatment of the host mouse with indomethacin, an inhibitor of cyclooxygenase-1 and cyclooxygenase-2, or with NS-398, a selective inhibitor of cyclooxygenase-2, resulted in (i) decreased PGE(2) levels, (ii) a decrease in neutrophil infiltration, (iii) a decrease in IL-8 production, and (iv) a decrease in the enhanced epithelial permeability seen with amebic infection. These results indicate that amebic infection in the colon induces the expression of cyclooxygenase-2 in epithelial cells and macrophages. Moreover, prostaglandins produced through cyclooxygenase-2 participate in the mediation of the neutrophil response to infection and enhance epithelial permeability.

Topics: Animals; Colon; Colonic Diseases; Cyclooxygenase 2; Dinoprostone; Entamoebiasis; Enzyme Induction; Humans; Interleukin-1; Interleukin-8; Isoenzymes; Membrane Proteins; Mice; Mice, SCID; NF-kappa B; Peroxidase; Prostaglandin-Endoperoxide Synthases

Pathogenic bacteria that penetrate the intestinal epithelial barrier stimulate an inflammatory response in the adjacent intestinal mucosa. The present studies asked whether colon epithelial cells can provide signals that are important for the initiation and amplification of an acute mucosal inflammatory response. Infection of monolayers of human colon epithelial cell lines (T84, HT29, Caco-2) with invasive strains of bacteria (Salmonella dublin, Shigella dysenteriae, Yersinia enterocolitica, Listeria monocytogenes, enteroinvasive Escherichia coli) resulted in the coordinate expression and upregulation of a specific array of four proinflammatory cytokines, IL-8, monocyte chemotactic protein-1, GM-CSF, and TNF alpha, as assessed by mRNA levels and cytokine secretion. Expression of the same cytokines was upregulated after TNF alpha or IL-1 stimulation of these cells. In contrast, cytokine gene expression was not altered after infection of colon epithelial cells with noninvasive bacteria or the noninvasive protozoan parasite, G. lamblia. Notably, none of the cell lines expressed mRNA for IL-2, IL-4, IL-5, IL-6, IL-12p40, IFN-gamma, or significant levels of IL-1 or IL-10 in response to the identical stimuli. The coordinate expression of IL-8, MCP-1, GM-CSF and TNF alpha appears to be a general property of human colon epithelial cells since an identical array of cytokines, as well as IL-6, also was expressed by freshly isolated human colon epithelial cells. Since the cytokines expressed in response to bacterial invasion or other proinflammatory agonists have a well documented role in chemotaxis and activation of inflammatory cells, colon epithelial cells appear to be programmed to provide a set of signals for the activation of the mucosal inflammatory response in the earliest phases after microbial invasion.

Topics: Animals; Bacterial Infections; Base Sequence; Cell Line; Chemokine CCL2; Chemotactic Factors; Colonic Diseases; Cytokines; Epithelial Cells; Epithelium; Gene Expression Regulation; Giardia lamblia; Giardiasis; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Inflammation; Interleukin-8; Molecular Sequence Data; RNA, Messenger; Tumor Necrosis Factor-alpha