Linked Life Data

18202115

Source:http://linkedlifedata.com/resource/pubmed/id/18202115

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-3-6
pubmed:abstractText
Interleukin-11 (IL-11) displays epithelial cytoprotective effects during intestinal injury. Antiapoptotic effects of IL-11 have been described, yet mechanisms remain unclear. Fas/CD95 death receptor signaling is upregulated in ulcerative colitis, leading to mucosal breakdown. We hypothesized that IL-11 inhibits Fas ligand (FasL)-mediated apoptosis in intestinal epithelia. Cell death was monitored in IEC-18 cells by microscopy, caspase and poly(ADP-ribose) polymerase cleavage, mitochondrial release of cytochrome c, and abundance of cytoplasmic oligonucleosomal DNA. RT-PCR was used to monitor Fas, cIAP1, cIAP2, XIAP, cFLIP, survivin, and Bcl-2 family members. Fas membrane expression was detected by immunoblot. Inhibitors of JAK2, phosphatidylinositol 3-kinase (PI3-kinase), Akt 1, MEK1 and MEK2, and p38 MAPK were used to delineate IL-11's antiapoptotic mechanisms. IL-11 did not alter Fas expression. Pretreatment with IL-11 for 24 h before FasL reduced cytoplasmic oligonucleosomal DNA by 63.2%. IL-11 also attenuated caspase-3, caspase-9, and poly(ADP-ribose) polymerase cleavage without affecting expression of activated caspase-8 p20 or cytochrome c release. IL-11 did not affect mRNA expression of the candidate antiapoptotic genes. The MEK1 and MEK2 inhibitors U-0126 and PD-98059 significantly attenuated the protection of IL-11 against caspase-3 and caspase-9 cleavage and cytoplasmic oligonucleosomal DNA accumulation. Although Akt inhibition reversed IL-11-mediated effects on caspase cleavage, it did not reverse the protective effects of IL-11 by DNA ELISA. We conclude that IL-11-dependent MEK1 and MEK2 signaling inhibits FasL-induced apoptosis. The lack of reversal of the IL-11 effect on DNA cleavage by Akt inhibition, despite antagonism of caspase cleavage, suggests that IL-11 inhibits caspase-independent cell death signaling by FasL in a MEK-dependent manner.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
294
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G728-37
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18202115-Animals, pubmed-meshheading:18202115-Apoptosis, pubmed-meshheading:18202115-Caspase 3, pubmed-meshheading:18202115-Caspase 9, pubmed-meshheading:18202115-Cell Membrane, pubmed-meshheading:18202115-Cells, Cultured, pubmed-meshheading:18202115-Cytosol, pubmed-meshheading:18202115-Data Interpretation, Statistical, pubmed-meshheading:18202115-Enzyme Inhibitors, pubmed-meshheading:18202115-Epithelial Cells, pubmed-meshheading:18202115-Fas Ligand Protein, pubmed-meshheading:18202115-Immunoblotting, pubmed-meshheading:18202115-Interleukin-11, pubmed-meshheading:18202115-Intestinal Mucosa, pubmed-meshheading:18202115-MAP Kinase Kinase Kinases, pubmed-meshheading:18202115-Mitochondria, pubmed-meshheading:18202115-Poly(ADP-ribose) Polymerases, pubmed-meshheading:18202115-Proto-Oncogene Proteins c-akt, pubmed-meshheading:18202115-Rats, pubmed-meshheading:18202115-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18202115-Signal Transduction
pubmed:year
2008
pubmed:articleTitle
Interleukin-11 antagonizes Fas ligand-mediated apoptosis in IEC-18 intestinal epithelial crypt cells: role of MEK and Akt-dependent signaling.
pubmed:affiliation
Department of Medicine, Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't