Increased monocyte TNF-alpha message stability contributes to trauma patients' increased TNF production
UMass Chan Affiliations
Department of Medicine, Division of GastroenterologyDocument Type
Journal ArticlePublication Date
1997-10-23Keywords
AdultAged
Aged, 80 and over
Animals
Biological Assay
Burns
Female
Humans
Inflammation
Male
Mice
Middle Aged
Monocytes
RNA, Messenger
Reference Values
Regression Analysis
*Transcription, Genetic
Tumor Necrosis Factor-alpha
Wounds and Injuries
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Post-trauma elevation of tumor necrosis factor alpha (TNF-alpha) appears to be critical in mediating many symptoms of systemic inflammatory response syndrome (SIRS), resulting in late mortality. Although increased monocyte (mphi) TNF-alpha production plays a pivotal role in this TNF-alpha elevation, the molecular mechanisms leading to increased mphi TNF-alpha production have yet to be elucidated. We demonstrate that, although TNF-alpha mRNA levels are increased in all trauma patients' mphi, which produce elevated levels of TNF-alpha protein, in the majority of patients, these increased TNF-alpha mRNA levels are under normal transcriptional and posttranscriptional control. Consequently, the increased TNF-alpha production by these patients' mphi is probably due to preactivation of these mphi by trauma-released mediators. However, a small minority of patients, whose mortality rate was 57%, produce TNF-alpha of primarily the membrane-associated type. The mphi TNF-alpha mRNA accumulation of these patients in response to in vitro stimulation is significantly augmented. All of these patients experienced SIRS. In this subset of patients' mphi, TNF-alpha mRNA stability was aberrantly increased. Such an increase in TNF-alpha mRNA stability could lead to devastatingly prolonged production of TNF-alpha protein. This demonstration of increased TNF-alpha mRNA stability in post-trauma mphi represents a novel correlation of elevated membrane-associated TNF-alpha protein, increased mortality, and a mechanism for this occurrence.Source
J Leukoc Biol. 1997 Oct;62(4):524-34.
DOI
10.1002/jlb.62.4.524Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38270PubMed ID
9335324Related Resources
ae974a485f413a2113503eed53cd6c53
10.1002/jlb.62.4.524