Abstract:
:Severe sepsis remains an important cause of death, particularly among trauma and burn patients. The severity of the systemic inflammatory response after trauma or burns and susceptibility to sepsis vary among individuals. One possible mechanism is through differential effects on glucocorticoid receptor (GR) expression by pro-inflammatory mediators (e.g. lipopolysaccharide signaling). In a mouse burn model, we demonstrated differential GR levels, size, and transcriptional activity in CD14 knockout (KO) mice when compared to wild-type (C57BL/6J) after injury. Sequence analysis revealed only 8 CAG repeats in the GR transactivation domain in the CD14 KO; the wild-type contained seventeen. A survey of genomic DNA from 51 mouse strains demonstrated CAG repeat length range from 7 - 17. We then studied the effect of polymorphism in CAG repeat length on GR activity. Fragments with CAG repeats varying from 8-40 (8, 17, 30, 38, and 40) were engineered and shuttled into the wild-type GR expression vector. The resulting plasmids were then co-transfected with a glucocorticoid response element linked to a luciferase in order to compare their transactivation potentials. Transactivation potential was highest in the 17-CAG GR. The effect of GR polymorphisms on GR activity warrants more research as this data suggests a mechanism for the individual differences in response to steroid treatment and the response to injury.
journal_name
Exp Mol Patholjournal_title
Experimental and molecular pathologyauthors
Yee KS,Cho K,Green T,Chandler J,Greenhalgh DGdoi
10.1016/j.yexmp.2008.04.003subject
Has Abstractpub_date
2008-06-01 00:00:00pages
200-5issue
3eissn
0014-4800issn
1096-0945pii
S0014-4800(08)00045-2journal_volume
84pub_type
杂志文章abstract::Angiogenesis is a common feature of pathological processes including wound healing, tumor formation, and chronic inflammation. Chronic inflammation can also be associated with dilation or proliferation of lymph vessels. We examined blood vessels and lymphatics and the expression of pro- and anti-angiogenic genes in th...
journal_title:Experimental and molecular pathology
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journal_title:Experimental and molecular pathology
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doi:10.1016/j.yexmp.2011.03.001
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pub_type: 杂志文章
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更新日期:1988-12-01 00:00:00
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