Interferon gamma downregulates IL-8 production in primary human colonic epithelial cells without induction of apoptosis
| Autor: | Daniela Vogl, Johannes Grossmann, Frank-Peter Wachs, Werner Falk, M. Maendel, Gerhard Rogler, T. Andus, J. Schölmerich, Klaus Schlottmann |
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| Rok vydání: | 2003 |
| Předmět: |
Colon
Cell Culture Techniques Down-Regulation Inflammation Antineoplastic Agents Apoptosis Inflammatory bowel disease Interferon-gamma Mediator medicine Humans Interferon gamma Interleukin 8 Intestinal Mucosa business.industry Interleukin-8 Gastroenterology Epithelial Cells medicine.disease Inflammatory Bowel Diseases digestive system diseases Epithelium medicine.anatomical_structure Immunology medicine.symptom Cell activation business medicine.drug |
| Zdroj: | International journal of colorectal disease. 19(5) |
| ISSN: | 0179-1958 |
| Popis: | In acute or chronic inflammatory bowel disease (IBD) interferon gamma (IFNgamma) is still considered to be an important pro-inflammatory mediator. In the present study we investigated the impact of IFNgamma on interleukin-8 (IL-8) production as a read-out for cell activation in intestinal epithelial cell (IEC) lines and primary human colonic epithelial cells (CEC).Primary cultures of human CEC were established from the mucosa of patients without inflammatory disease. CEC, HT-29 or Caco-2 cells were incubated with either IFNgamma, tumor necrosis factor (TNF)alpha or IL-10. IL-8 and IL-1Ra secretion was determined by ELISA. Competicon PCR was used for quantification of IL-8mRNA. Apoptosis was quantified by propidium iodine incorporation and fluorescence activated cell sorting (FACS) analysis.In contrast to HT-29 cells in primary human CEC 100 U/ml IFNgamma inhibited IL-8 secretion significantly to 70+/-15% of unstimulated primary CEC (p0.005) more effectively than IL-10 (87+/-21% versus unstimulated cells, n.s.). In HT-29 cells, IL-8 secretion was induced to 405+/-101% of unstimulated cells. In Caco-2 cells, IFNgamma had no significant effect on IL-8 secretion. The effect in HT-29 and CEC was concentration dependent. In primary CEC, 200 U/ml IFNgamma further reduced IL-8 secretion to 48+/-18% of unstimulated CEC (p0.05). Whereas IL-8 mRNA was strongly upregulated in HT-29 cells, no upregulation or even a downregulation was found in CEC. Pre-incubation with 100 U/ml IFNgamma did not increase the susceptibility to apoptosis mediated by anti-Fas antibody (CH-11) in primary CEC, whereas HT-29 cells showed increased rates of apoptosis after priming with IFNgamma.In contrast to HT-29, IFNgamma downregulated IL-8 secretion and did not induce IL-8 mRNA expression in primary human CEC. This effect was not due to induction of apoptosis. |
| Databáze: | OpenAIRE |
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