Linked Life Data

20671197

Source:http://linkedlifedata.com/resource/pubmed/id/20671197

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-9-29
pubmed:abstractText
Neutrophils and their chemoattractants, the CXC-ELR chemokines keratinocyte cytokine (KC) and macrophage inflammatory protein-2 (MIP-2), play a critical role in pancreatitis. While acute pancreatitis is initiated in acinar cells, it is unclear if these are a source of CXC-ELR chemokines. KC and MIP-2 have NF-?B, activator protein-1 (AP-1) sites in their promoter regions. However, previous studies have shown increased basal and reduced caerulein-induced AP-1 activation in harvested pancreatic tissue in vitro, which limits interpreting the caerulein-induced response. Moreover, recent studies suggest that NF-?B silencing in acinar cells alone may not be sufficient to reduce inflammation in acute pancreatitis. Thus the aim of this study was to determine whether acinar cells are a source of KC and MIP-2 and to understand their transcriptional regulation. Primary overnight-cultured murine pancreatic acini were used after confirming their ability to replicate physiological and pathological acinar cell responses. Upstream signaling resulting in KC, MIP-2 upregulation was studied along with activation of the transcription factors NF-?B and AP-1. Cultured acini replicated critical responses to physiological and pathological caerulein concentrations. KC and MIP-2 mRNA levels increased in response to supramaximal but not to physiological caerulein doses. This upregulation was calcium and protein kinase C (PKC), but not cAMP, dependent. NF-?B inhibition completely prevented upregulation of KC but not MIP-2. Complete suppression of MIP-2 upregulation required dual inhibition of NF-?B and AP-1. Acinar cells are a likely source of KC and MIP-2 upregulation during pancreatitis. This upregulation is dependent on calcium and PKC. MIP-2 upregulation requires both NF-?B and AP-1 in these cells. Thus dual inhibition of NF-?B and AP-1 may be a more successful strategy to reduce inflammation in pancreatitis than targeting NF-?B alone.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/9-deoxy-delta-9-prostaglandin D2, http://linkedlifedata.com/resource/pubmed/chemical/Caerulein, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL1, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL2, http://linkedlifedata.com/resource/pubmed/chemical/Cxcl1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cxcl2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin D2, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1522-1547
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G867-76
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Transcriptional regulation of CXC-ELR chemokines KC and MIP-2 in mouse pancreatic acini.
pubmed:affiliation
Dept. of Medicine, Univ. of Pittsburgh, PA 15213, USA. Singhv2@upmc.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural