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Differential expression and polarized secretion of CXC and CC chemokines by human intestinal epithelial cancer cell lines in response to Clostridium difficile toxin A

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Authors
Kim, Jung Mogg; Kim, Joo Sung; Jun, Hyun Chae; Oh, Yu-Kyoung; Song, In Sung; Kim, Chung Yong
Issue Date
2002-07-26
Publisher
Blackwell Publishing
Citation
Microbiol Immunol. 2002;46(5):333-42.
Keywords
Bacterial Toxins/*pharmacologyCaco-2 CellsChemokine CCL2/biosynthesis/genetics/*secretionChemokine CCL3Chemokine CCL4Chemokine CCL5/genetics/metabolismChemokines, CXC/biosynthesis/genetics/*secretionClostridium difficile/*metabolismEnterotoxins/*pharmacologyEnzyme-Linked Immunosorbent AssayHT29 CellsHumansIntestinal Mucosa/drug effects/metabolism/microbiology/*secretionL-Lactate Dehydrogenase/metabolismMacrophage Inflammatory Proteins/genetics/metabolismPyrimidinones/metabolismRNA, Messenger/chemistry/geneticsReverse Transcriptase Polymerase Chain ReactionThiazolesUp-Regulation
Abstract
Intestinal epithelial cells are the initial sites of host response to Clostridium difficile infection and can play a role in signaling the influx of inflammatory cells. To further explore this role, the regulated expression and polarized secretion of CXC and CC chemokines by human intestinal epithelial cells were investigated. An expression of the CXC chemokines, including IL-8 and growth-related oncogene (GRO)-alpha, and the CC chemokine monocyte chemoattractant protein (MCP)-1 from HT-29 cells increased in the 1-6 hr following C. difficile toxin A stimulation, assessed by quantitative RT-PCR. In contrast, the expression of neutrophil activating protein-78 (ENA-78) was delayed for 18 hr. The up-regulated mRNA expression of chemokines was paralleled by the increase of protein levels. However, the expression of macrophage inflammatory protein (MIP)-1alpha, RANTES (regulated on activation normal T cells expressed and secreted), and interferon-gamma-inducible protein-10 (IP-10) was not changed in HT-29 or Caco-2 cells stimulated with toxin A. Upon stimulation of the polarized Caco-2 epithelial cells in a transwell chamber with toxin A, CXC and CC chemokines were released predominantly into the basolateral compartment. Moreover, the addition of IFN-gamma and TNF-alpha to toxin A stimulated Caco-2 cells increased the basolateral release of CC chemokine MCP-1. In contrast, IFN-gamma and TNF-alpha had no effect on the expression of the CXC chemokines IL-8 and GRO-alpha. These results suggest that a CXC and CC chemokine expression from epithelial cells infected with C. difficile may be an important factor in the mucosal inflammatory response.
ISSN
0385-5600 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12139393

http://hdl.handle.net/10371/11791
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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