Source:http://linkedlifedata.com/resource/pubmed/id/17015748
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2006-10-3
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pubmed:abstractText |
To better predict the consequences of blocking signal transduction pathways as a means of controlling intestinal inflammation, we are characterizing the pathways up-regulated by IL-1 in intestinal epithelial cells (IEC). IL-1beta induced increased mRNA levels of MIP-2, MCP-1, RANTES, inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) in the IEC-18 cell line. IL-1beta activated NF-kappaB but not ERK or p38. Infecting cells with adenovirus expressing a mutated gene for IkappaBalpha (IkappaBAA) blocked IL-1-induced mRNA increases in MIP-2, MCP-1, and iNOS but not COX-2 or RANTES. Expression of IkappaBAA attenuated the IL-1-induced increase in COX-2 protein. Unexpectedly, RANTES mRNA increased, and protein was secreted by cells expressing IkappaBAA in the absence of IL-1. Adenovirus-expressing IkappaBAA, blocking protein synthesis, and IL-1beta all resulted in activation of JNK. The JNK inhibitor SP600125 prevented the RANTES increases by all three stimuli. A human enterocyte line was similarly examined, and both NF-kappaB and JNK regulate IL-1-induced RANTES secretion. We conclude that in IEC-18, IL-1beta-induced increases in mRNA for MIP-2, MCP-1, and iNOS are NF-kappaB-dependent, whereas regulation of RANTES mRNA is independent of NF-kappaB but is positively regulated by JNK. IL-1beta-induced mRNA increases in COX-2 mRNA are both NF-kappaB- and MAPK-independent but the translation of COX-2 protein is NF-kappaB-dependent. This pattern of signaling due to a single stimulus exposed the complexities of regulating inflammatory genes in IEC.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
177
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5604-11
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17015748-Cell Line,
pubmed-meshheading:17015748-Cyclooxygenase 2,
pubmed-meshheading:17015748-Epithelial Cells,
pubmed-meshheading:17015748-Erythrocytes,
pubmed-meshheading:17015748-Gene Expression Regulation,
pubmed-meshheading:17015748-Humans,
pubmed-meshheading:17015748-Inflammation,
pubmed-meshheading:17015748-Interleukin-1,
pubmed-meshheading:17015748-Intestinal Mucosa,
pubmed-meshheading:17015748-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:17015748-Membrane Proteins,
pubmed-meshheading:17015748-NF-kappa B,
pubmed-meshheading:17015748-RNA, Messenger,
pubmed-meshheading:17015748-Signal Transduction,
pubmed-meshheading:17015748-Up-Regulation
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pubmed:year |
2006
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pubmed:articleTitle |
Differential pattern of inflammatory molecule regulation in intestinal epithelial cells stimulated with IL-1.
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pubmed:affiliation |
Department of Pediatrics, Dalhousie Universiy, Halifax, Nova Scotia, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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