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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-3-31
pubmed:abstractText
Many studies suggest that adenosine modulates cell responses in a wide array of tissues through potent and selective regulation of cytokine production. This study examined the effects of adenosine on interleukin (IL)-6 expression and its related signal pathways in mouse embryonic stem (ES) cells. In this study, the adenosine analogue 5'-N-ethylcarboxamide (NECA) increased IL-6 protein expression level. Mouse ES cells expressed the A(1), A(2A), A(2B), and A(3) adenosine receptors (ARs), whose expression levels were increased by NECA and NECA-induced increase of IL-6 mRNA expression or secretion level was inhibited by the non-specific AR inhibitor, caffeine. NECA increased Akt and protein kinase C (PKC) phosphorylation, intracellular Ca(2+) and cyclic adenosine monophosphate (cAMP) levels, which were blocked by caffeine. On the other hand, NECA-induced IL-6 secretion was partially inhibited by Akt inhibitor, bisindolylmaleimide I (PKC inhibitor), SQ 22536 (adenylate cyclate inhibitor) and completely blocked by the 3 inhibitor combination treatment. In addition, NECA increased mitogen activated protein kinase' (MAPK) phosphorylation, which were partially inhibited by the Akt inhibitor, bisindolylmaleimide I, and SQ 22536 and completely blocked by the 3 inhibitor combination treatment. NECA-induced increases of IL-6 protein expression and secretion levels were inhibited by MAPK inhibition. NECA-induced increase of nuclear factor (NF)-kappaB phosphorylation was inhibited by MAPK inhibitors. NECA also increased cAMP response element-binding protein (CREB) phosphorylation, which was blocked by MAPK or NF-kappaB inhibitors. Indeed, NECA-induced increase of IL-6 protein expression and secretion was blocked by NF-kappaB inhibitors. In conclusion, NECA stimulated IL-6 expression via MAPK and NF-kappaB activation through Akt, Ca(2+)/PKC, and cAMP signaling pathways in mouse ES cells. J. Cell. Physiol. 219: 752-759, 2009. (c) 2009 Wiley-Liss, Inc.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1097-4652
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
219
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
752-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
5'-N-ethylcarboxamide induces IL-6 expression via MAPKs and NF-kappaB activation through Akt, Ca(2+)/PKC, cAMP signaling pathways in mouse embryonic stem cells.
pubmed:affiliation
Department of Veterinary Physiology, Biotherapy Human Resources Center (BK 21), College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't