Interferon γ induces differential upregulation of α and β chemokine secretion in colonic epithelial cell lines
Autor: | S J Hopkins, Geoffrey Warhurst, A C Warhurst |
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Rok vydání: | 1998 |
Předmět: |
Chemokine
medicine.medical_specialty Chemokine CXCL1 medicine.medical_treatment Gene Expression CCL2 CCL7 Immunoenzyme Techniques Interferon-gamma Internal medicine medicine Humans RNA Messenger Interleukin 8 Growth Substances Chemokine CCL5 Macrophage inflammatory protein Chemokine CCL2 Chemotactic Factors Dose-Response Relationship Drug biology Tumor Necrosis Factor-alpha Interleukin-8 Gastroenterology Drug Synergism Cell Biology Molecular biology Beta Chemokine Growth Inhibitors Stimulation Chemical Endocrinology Cytokine Chemokine secretion biology.protein Intercellular Signaling Peptides and Proteins Caco-2 Cells Chemokines Chemokines CXC HT29 Cells |
Zdroj: | Scopus-Elsevier |
ISSN: | 1468-3288 0017-5749 |
DOI: | 10.1136/gut.42.2.208 |
Popis: | Background—Production of chemoattractant factors by the intestinal epithelium may contribute to mucosal infiltration by inflammatory cells in inflammatory bowel disease. Secretion of the α chemokine interleukin 8 (IL-8), a neutrophil chemoattractant, has been widely studied, but little is known about epithelial secretion of β chemokines, which are preferentially involved in recruiting monocytes.Aims—To investigate the profiles of α and β chemokine secretion in colonic cell lines and their differential modulation by interferon γ (IFN-γ), a product of activated T lymphocytes and natural killer cells.Methods and results—HT29-19A, a model of the Cl− secretory crypt cell, exhibited a parallel secretion of the α chemokines IL-8 and GROα, which could be markedly upregulated by tumour necrosis factor α (TNF-α) and IL-1β. These cells showed no significant expression of the β chemokines RANTES (regulated upon activation T cell expressed and secreted), MIP-1α (macrophage inflammatory protein 1α), and MCP-1 (monocyte chemotactic protein 1) under these conditions, but IFN-γ in combination with TNF-α caused a dose dependent induction of RANTES and MCP-1 secretion. This was accompanied by a marked increase of RANTES mRNA. In contrast, IFN-γ had no significant effect on TNF-α stimulated IL-8 secretion. Caco-2 cells, with features more typical of villus absorptive cells, were relatively poor secretors of α chemokines but secreted high levels of MCP-1 in response to IL-1β. IFN-γ did not influence α or β chemokine secretion in these cells.Conclusions—These studies suggest that intestinal epithelial cells may produce chemokines capable of attracting both neutrophils and monocytes. The ability of IFN-γ to activate the expression of β chemokines preferentially could facilitate the development of chronic inflammatory infiltrates. |
Databáze: | OpenAIRE |
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