Interferon-gamma sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosis.

Hdl Handle:
http://hdl.handle.net/10147/209102
Title:
Interferon-gamma sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosis.
Authors:
O'Connell, J; Bennett, M W; Nally, K; O'Sullivan, G C; Collins, J K; Shanahan, F
Affiliation:
Department of Medicine, Cork University Hospital, National University of Ireland,, Cork, Ireland. j.oconnell@ucc.ie
Citation:
J Cell Physiol. 2000 Dec;185(3):331-8.
Journal:
Journal of cellular physiology
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209102
DOI:
10.1002/1097-4652(200012)185:3<331::AID-JCP3>3.0.CO;2-V
PubMed ID:
11056003
Abstract:
Homeostasis in the colonic epithelium is achieved by a continuous cycle of proliferation and apoptosis, in which imbalances are associated with disease. Inflammatory bowel disease (IBD) and colon cancer are associated with either excessive or insufficient apoptosis of colonic epithelial cells, respectively. By using two colonic epithelial cell lines, HT29 and SW620, we investigated how the epithelial cell's sensitivity to apoptosis was regulated by the proinflammatory cytokine interferon-gamma (IFN-gamma). We found that IFN-gamma sensitized HT29 cells, and to a lesser extent SW620, to diverse inducers of apoptosis of physiologic or therapeutic relevance to the colon. These apoptosis inducers included Fas (CD95/APO-1) ligand (FasL), short-chain fatty acids, and chemotherapeutic drugs. The extent of IFN-gamma-mediated apoptosis sensitization in these two cell lines correlated well with the degree of IFN-gamma-mediated upregulation of the proapoptotic protease caspase-1. Although IFN-gamma alone effectively sensitized HT29 cells to apoptosis, inclusion of the protein synthesis inhibitor cyclohexamide (CHX) during apoptotic challenge was necessary for maximal sensitization of SW620. The requirement of CHX to sensitize SW620 cells to apoptosis implies a need to inhibit translation of antiapoptotic proteins absent from HT29. In particular, the antiapoptotic protein Bcl-2 was strongly expressed in SW620 cells but absent from HT29. Our results indicate that IFN-gamma increases the sensitivity of colonic epithelial cells to diverse apoptotic stimuli in concert, via upregulation of caspase-1. Our findings implicate caspase-1 and Bcl-2 as important central points of control determining the general sensitivity of colonic epithelial cells to apoptosis.
Language:
eng
MeSH:
Antineoplastic Agents/*pharmacology; Apoptosis/*drug effects; Cell Line; Colon/drug effects/*pathology; Drug Synergism; Fas Ligand Protein; Fatty Acids, Volatile/pharmacology; Humans; Interferon-gamma/*pharmacology; Intestinal Mucosa/drug effects/*pathology; Membrane Glycoproteins/pharmacology
ISSN:
0021-9541 (Print); 0021-9541 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Connell, Jen_GB
dc.contributor.authorBennett, M Wen_GB
dc.contributor.authorNally, Ken_GB
dc.contributor.authorO'Sullivan, G Cen_GB
dc.contributor.authorCollins, J Ken_GB
dc.contributor.authorShanahan, Fen_GB
dc.date.accessioned2012-02-03T15:12:20Z-
dc.date.available2012-02-03T15:12:20Z-
dc.date.issued2012-02-03T15:12:20Z-
dc.identifier.citationJ Cell Physiol. 2000 Dec;185(3):331-8.en_GB
dc.identifier.issn0021-9541 (Print)en_GB
dc.identifier.issn0021-9541 (Linking)en_GB
dc.identifier.pmid11056003en_GB
dc.identifier.doi10.1002/1097-4652(200012)185:3<331::AID-JCP3>3.0.CO;2-Ven_GB
dc.identifier.urihttp://hdl.handle.net/10147/209102-
dc.description.abstractHomeostasis in the colonic epithelium is achieved by a continuous cycle of proliferation and apoptosis, in which imbalances are associated with disease. Inflammatory bowel disease (IBD) and colon cancer are associated with either excessive or insufficient apoptosis of colonic epithelial cells, respectively. By using two colonic epithelial cell lines, HT29 and SW620, we investigated how the epithelial cell's sensitivity to apoptosis was regulated by the proinflammatory cytokine interferon-gamma (IFN-gamma). We found that IFN-gamma sensitized HT29 cells, and to a lesser extent SW620, to diverse inducers of apoptosis of physiologic or therapeutic relevance to the colon. These apoptosis inducers included Fas (CD95/APO-1) ligand (FasL), short-chain fatty acids, and chemotherapeutic drugs. The extent of IFN-gamma-mediated apoptosis sensitization in these two cell lines correlated well with the degree of IFN-gamma-mediated upregulation of the proapoptotic protease caspase-1. Although IFN-gamma alone effectively sensitized HT29 cells to apoptosis, inclusion of the protein synthesis inhibitor cyclohexamide (CHX) during apoptotic challenge was necessary for maximal sensitization of SW620. The requirement of CHX to sensitize SW620 cells to apoptosis implies a need to inhibit translation of antiapoptotic proteins absent from HT29. In particular, the antiapoptotic protein Bcl-2 was strongly expressed in SW620 cells but absent from HT29. Our results indicate that IFN-gamma increases the sensitivity of colonic epithelial cells to diverse apoptotic stimuli in concert, via upregulation of caspase-1. Our findings implicate caspase-1 and Bcl-2 as important central points of control determining the general sensitivity of colonic epithelial cells to apoptosis.en_GB
dc.language.isoengen_GB
dc.subject.meshAntineoplastic Agents/*pharmacologyen_GB
dc.subject.meshApoptosis/*drug effectsen_GB
dc.subject.meshCell Lineen_GB
dc.subject.meshColon/drug effects/*pathologyen_GB
dc.subject.meshDrug Synergismen_GB
dc.subject.meshFas Ligand Proteinen_GB
dc.subject.meshFatty Acids, Volatile/pharmacologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInterferon-gamma/*pharmacologyen_GB
dc.subject.meshIntestinal Mucosa/drug effects/*pathologyen_GB
dc.subject.meshMembrane Glycoproteins/pharmacologyen_GB
dc.titleInterferon-gamma sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosis.en_GB
dc.contributor.departmentDepartment of Medicine, Cork University Hospital, National University of Ireland,, Cork, Ireland. j.oconnell@ucc.ieen_GB
dc.identifier.journalJournal of cellular physiologyen_GB
dc.description.provinceMunster-

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