interleukin-8 and Giardiasis

Globally, there are greater than 700,000 deaths per year associated with diarrheal disease. The flagellated intestinal parasite, Giardia lamblia, is one of the most common intestinal pathogens in both humans and animals throughout the world. While attached to the gastrointestinal epithelium, Giardia induces epithelial cell apoptosis, disrupts tight junctions, and increases intestinal permeability. The underlying cellular and molecular mechanisms of giardiasis, including the role lamina propria immune cells, such as macrophages, play in parasite control or clearance are poorly understood. Thus far, one of the major obstacles in ascertaining the mechanisms of Giardia pathology is the lack of a functionally relevant model for the long-term study of the parasite in vitro. Here we report on the development of an in vitro co-culture model which maintains the basolateral-apical architecture of the small intestine and allows for long-term survival of the parasite. Using transwell inserts, Caco-2 intestinal epithelial cells and IC-21 macrophages are co-cultured in the presence of Giardia trophozoites. Using the developed model, we show that Giardia trophozoites survive over 21 days and proliferate in a combination media of Caco-2 cell and Giardia medium. Giardia induces apoptosis of epithelial cells through caspase-3 activation and macrophages do not abrogate this response. Additionally, macrophages induce Caco-2 cells to secrete the pro-inflammatory cytokines, GRO and IL-8, a response abolished by Giardia indicating parasite induced suppression of the host immune response. The co-culture model provides additional complexity and information when compared to a single-cell model. This model will be a valuable tool for answering long-standing questions on host-parasite biology that may lead to discovery of new therapeutic interventions.

Topics: Animals; Apoptosis; Caco-2 Cells; Caspase 3; Chemokine CXCL1; Coculture Techniques; Epithelial Cells; Giardia lamblia; Giardiasis; Humans; Interleukin-8; Intestinal Mucosa; Macrophages, Peritoneal; Mice; Models, Biological

The evaluation of eosinophil cationic protein (ECP) concentration--one of late allergy reaction markers was performed in serum of children with food allergy and children with food allergy and H. pylori or Giardia lamblia infection of the gastrointestinal tract. The ECP values were referred to the characteristics of histopathological changes in gastric mucosa and to the values of cytokines (IL-4, IL-5, IL-8) determined in biopsy specimens of gastric mucosa from these patients. The studies indicate that the exclusive evaluation of ECP concentration in serum does not reflect unequivocally the severity of pathological changes of gastric mucosa in children with food allergy.

Topics: Adolescent; Blood Proteins; Case-Control Studies; Child; Enzyme-Linked Immunosorbent Assay; Eosinophil Granule Proteins; Female; Food Hypersensitivity; Gastric Mucosa; Giardiasis; Helicobacter Infections; Humans; Inflammation Mediators; Interleukin-4; Interleukin-5; Interleukin-8; Intestinal Mucosa; Male; Ribonucleases

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