Linked Life Data

17138860

Source:http://linkedlifedata.com/resource/pubmed/id/17138860

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-12-1
pubmed:abstractText
TNF is implicated in the suppression of neutrophil apoptosis during sepsis. Multiple signaling pathways are involved in TNF-mediated antiapoptotic signaling; a role for the MAP kinases (MAPK), ERK1/2, and p38 MAPK has been suggested. Antiapoptotic signaling is mediated principally through TNF receptor-1 (TNFR-1), and the PKC isotype-delta (delta-PKC) is a critical regulator of TNFR-1 signaling. delta-PKC associates with TNFR-1 in response to TNF and is required for NFkappaB activation and inhibition of caspase 3. The role of delta-PKC in TNF-mediated activation of MAPK is not known. The purpose of this study was to determine whether the MAPK, ERK1/2, and p38 MAPK are involved in TNF antiapoptotic signaling and whether delta-PKC is a key regulator of MAPK activation by TNF. In human neutrophils, TNF activated both p38 MAPK and ERK1/2 principally via TNFR-1. The MEK1/2 inhibitors PD098059 and U0126, but not the p38 MAPK inhibitor SB203580, decreased TNF antiapoptotic signaling as measured by caspase 3 activity. A specific delta-PKC antagonist, V1.1delta-PKC-Tat peptide, inhibited TNF-mediated ERK1/2 activation, but not p38 MAPK. ERK1/2 inhibition did not alter recruitment of delta-PKC to TNFR-1, indicating delta-PKC is acting upstream of ERK1/2. In HL-60 cells differentiated to a neutrophilic phenotype, delta-PKC depletion by delta-PKC siRNA resulted in inhibition of TNF mediated ERK1/2 activation but not p38 MAPK. Thus, ERK1/2, but not p38 MAPK, is an essential component of TNF-mediated antiapoptotic signaling. In human neutrophils, delta-PKC is a positive regulator of ERK1/2 activation via TNFR-1 but has no role in p38 MAPK activation.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0741-5400
pubmed:author
pubmed:issnType
Print
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1512-21
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Regulation of TNF mediated antiapoptotic signaling in human neutrophils: role of delta-PKC and ERK1/2.
pubmed:affiliation
Department of Pediatrics, University of Pennsylvania School of Medicine and the Joseph Stokes Jr. Research Institute, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. kilpatrick@email.chop.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural