pubmed-article:12183528 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0035589 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0085828 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0225336 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0024432 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0033684 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0017337 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0008013 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0040648 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0162493 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0679058 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C1547699 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
pubmed-article:12183528 | lifeskim:mentions | umls-concept:C2700640 | lld:lifeskim |
pubmed-article:12183528 | pubmed:issue | 9 | lld:pubmed |
pubmed-article:12183528 | pubmed:dateCreated | 2002-8-16 | lld:pubmed |
pubmed-article:12183528 | pubmed:abstractText | Human macrophage chemoattractant protein 1 (MCP-1) is a potent mediator of macrophage migration and therefore plays an essential role in early events of inflammation. In endothelial cells, at least three independent pathways regulate MCP-1 expression by NF-kappaB and AP-1. Orientia tsutsugamushi causes vasculitis in humans by replicating inside macrophages and endothelial cells. In the present study, we investigated the cis-acting and trans-acting elements involved in O. tsutsugamushi-induced MCP-1 gene expression in human umbilical vein endothelial cells (HUVEC). Although NF-kappaB activation was observed in HUVEC infected with O. tsutsugamushi, inhibition of NF-kappaB activation did not affect the MCP-1 expression. However, treatment of HUVEC with extracellular signal-regulated kinase (ERK) kinase inhibitor or p38 mitogen-activated protein kinase (MAPK) inhibitor suppressed expression of MCP-1 mRNA concomitant with downregulation of activator protein 1 (AP-1) activation. Deletion of triphorbol acetate response elements (TRE) at position -69 to -63 of MCP-1 gene abolished inducible promoter activity. Deletion of TRE at position -69 to -63-96 to -90 or deletion of NF-kappaB-binding site at position -69 to -63-88 to -79 did not affect the inducibility of promoter. Site-directed mutagenesis of the NF-kappaB binding sites at positions -2640 to -2632, -2612 to -2603 in the enhancer region, or the AP-1 biding site at position -2276 to -2270 decreased the inducible activity of the promoter. Taken together, AP-1 activation by both the ERK pathway and the p38 MAPK pathway as well as their binding to TRE at position -69 to -63 in proximal promoter and TRE at position -2276 to -2270 in enhancer region is altogether essential in induction of MCP-1 mRNA in HUVEC infected with O. tsutsugamushi. Although NF-kappaB activation is not essential per se, the kappaB site in the enhancer region is important in MCP-1 induction of HUVEC. This discrepancy in the involvement of the NF-kappaB may be due to the function of chromatin structures and other transcription cofactors in the regulation of MCP-1 gene expression in response to O. tsutsugamushi infectioin. | lld:pubmed |
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pubmed-article:12183528 | pubmed:language | eng | lld:pubmed |
pubmed-article:12183528 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12183528 | pubmed:citationSubset | IM | lld:pubmed |
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pubmed-article:12183528 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:12183528 | pubmed:month | Sep | lld:pubmed |
pubmed-article:12183528 | pubmed:issn | 0019-9567 | lld:pubmed |
pubmed-article:12183528 | pubmed:author | pubmed-author:SeongSeung-Yo... | lld:pubmed |
pubmed-article:12183528 | pubmed:author | pubmed-author:ChoNam-HyukNH | lld:pubmed |
pubmed-article:12183528 | pubmed:author | pubmed-author:HuhMyung-Sook... | lld:pubmed |
pubmed-article:12183528 | pubmed:author | pubmed-author:KimNa-HyunNH | lld:pubmed |