interleukin-8 and chloramine

Gastric inflammation is a highly complex biochemical protective response to cellular/tissue injury. When this process occurs in an uncontrolled manner, the result is excessive cellular/tissue damage that results chronic inflammation and destruction of normal tissue. Current evidence suggests that Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) ingestion are major causative factors in the pathogenesis of gastric mucosal injury in humans. In response to H. pylori infection or NSAID, neutrophils are recruited to the site of inflammation and generate reactive oxygen and nitrogen species and proteases. However, neutrophils are not able to kill the bacteria that live in the gastric mucus, and compounds produced by activated neutrophils themselves may be potentially harmful for normal tissue. It has been shown that leukocyte-vascular endothelial cell interaction is regulated by various cell adhesion molecules, and that this interaction is directly or indirectly modified by many factors, the origin of which is H. pylori and NSAIDs. This review describes the potential role of neutrophils and neutrophil-associated inflammation for gastric oxidative stress and injury induced by H. pylori and/or NSAID.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Adhesion Molecules; Chloramines; Endothelium, Vascular; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Neutrophils

Sustained expression of cytoprotective intestinal epithelial heat shock proteins (Hsps), particularly Hsp27, depends on stimuli derived from bacterial flora. In this study, we examined the role of the bacterial chemotactic peptide fMLP in stimulating colonic epithelial Hsp expression at concentrations encountered in a physiological milieu. Treatment of the polarized human intestinal epithelial cell line Caco2bbe with physiological concentrations of fMLP (10-100 nM) induced expression of Hsp27, but not Hsp72, in a time- and concentration-dependent manner. Induction of Hsp27 by fMLP was specific since the fMLP analogs MRP and MLP were not effective. Hsp27 induction by fMLP was blocked by the fMLP-receptor antagonist BOC-FLFLF and was blocked when the dipeptide transporter PepT1, an entry pathway for fMLP, was silenced. fMLP activated both the p38 and ERK1/2 MAP kinase pathways in Caco2bbe cells, but not the SAPK/JNK pathway. The p38 inhibitor SB203580, but not the MEK-1 inhibitor PD98059, blocked Hsp27 induction by fMLP. fMLP treatment inhibited actin depolymerization and decreased transepithelial resistance caused by the oxidant monochloramine, and this inhibition was reversed by silencing Hsp27 expression. fMLP pretreatment also inhibited activation of proinflammatory transcription factor NF-kappaB by TNF-alpha in Caco2bbe cells, reducing induction of NF-kappaB target genes by TNF-alpha both in human intestinal biopsies and Caco2bbe cells. In conclusion, fMLP may contribute to the maintenance of intestinal homeostasis by mediating physiological expression of Hsp27, enhancing cellular protection, and negatively regulating the inflammatory response.

Topics: Actins; Caco-2 Cells; Chloramines; Cytoprotection; Dose-Response Relationship, Drug; Electric Impedance; Epithelial Cells; Female; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; Humans; Interleukin-8; Intestinal Mucosa; Male; MAP Kinase Signaling System; Middle Aged; Molecular Chaperones; N-Formylmethionine Leucyl-Phenylalanine; Neoplasm Proteins; NF-kappa B; Oligopeptides; Peptide Transporter 1; Protein Kinase Inhibitors; Receptors, Formyl Peptide; RNA Interference; RNA, Messenger; RNA, Small Interfering; Symporters; Time Factors; Tissue Culture Techniques; Transcription, Genetic; Tumor Necrosis Factor-alpha; Up-Regulation