Show simple item record

dc.contributor.authorFurse, Robert K.
dc.contributor.authorKodys, Karen
dc.contributor.authorZhu, Dan
dc.contributor.authorMiller-Graziano, Carol L.
dc.date2022-08-11T08:09:31.000
dc.date.accessioned2022-08-23T16:34:10Z
dc.date.available2022-08-23T16:34:10Z
dc.date.issued1997-10-23
dc.date.submitted2009-03-10
dc.identifier.citation<p>J Leukoc Biol. 1997 Oct;62(4):524-34.</p>
dc.identifier.issn0741-5400 (Print)
dc.identifier.doi10.1002/jlb.62.4.524
dc.identifier.pmid9335324
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38270
dc.description.abstractPost-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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=9335324&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1002/jlb.62.4.524
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectAnimals
dc.subjectBiological Assay
dc.subjectBurns
dc.subjectFemale
dc.subjectHumans
dc.subjectInflammation
dc.subjectMale
dc.subjectMice
dc.subjectMiddle Aged
dc.subjectMonocytes
dc.subjectRNA, Messenger
dc.subjectReference Values
dc.subjectRegression Analysis
dc.subject*Transcription, Genetic
dc.subjectTumor Necrosis Factor-alpha
dc.subjectWounds and Injuries
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleIncreased monocyte TNF-alpha message stability contributes to trauma patients' increased TNF production
dc.typeArticle
dc.source.journaltitleJournal of leukocyte biology
dc.source.volume62
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1143
dc.identifier.contextkey770121
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/1143
dc.contributor.departmentDepartment of Medicine, Division of Gastroenterology
dc.source.pages524-34


This item appears in the following Collection(s)

Show simple item record