a Record control number WOS:000292290100024

a ISSN 1932-6203

a Original cataloging agency NEU GrandLibrary

a Language code of text/sound track or separate title eng

a Classification number QZ140

b Item number .I4 2011

a Personal name Moran, Ana.

h Medium Electronic Document

a Title IL-6-Mediated Activation of Stat3 alpha Prevents Trauma/Hemorrhagic Shock-Induced Liver Inflammation

c Statement of responsibility, etc Ana Moran, Stephen A. Thacker, Ayse Akcan Arikan, Mary-Ann A. Mastrangelo, Yong Wu, Bi Yu, David J. Tweardy.

a Place of publication, distribution, etc Public library science,

c Date of publication, distribution, etc 2011.

a Summary, etc Trauma complicated by hemorrhagic shock (T/HS) is the leading cause of morbidity and mortality in the United States for individuals under the age of 44 years. Initial survivors are susceptible to developing multiple organ failure (MOF), which is thought to be caused, at least in part, by excessive or maladaptive activation of inflammatory pathways. We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required, and the mechanism(s) for the IL-6 protective effect have not been reported. In the experiments described here, we demonstrated that the extent of liver inflammation induced by T/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver inflammation and is associated with increased Stat3 activation. Global assessment of the livers showed that the main effect of IL-6 was to normalize the T/HS-induced inflammation transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver inflammation and to normalize the T/HS-induced liver inflammation transcriptome. Genetic deletion of a Stat3 beta, a naturally occurring, dominant-negative isoform of the Stat3, attenuated T/HS-induced liver inflammation, confirming a role for Stat3, especially Stat3 alpha, in preventing T/HS-mediated liver inflammation. Thus, T/HS-induced liver inflammation depends on the duration of hypotension and requires resuscitation; IL-6 administration at the start of resuscitation reverses T/HS-induced liver inflammation, through activation of Stat3 alpha, which normalized the T/HS-induced liver inflammation transcriptome.

a Topical term or geographic name as entry element Multiple organ failure

a Topical term or geographic name as entry element Near East University Article

a Topical term or geographic name as entry element Yakın Doğu Üniversitesi Makale

a Main entry heading Plos one

g Relationship information JUN 29 2011, Vol 6 Issue 6 Article Number: e21449

x International Standard Serial Number 19326203

u Uniform Resource Identifier http://library.neu.edu.tr:2048/login?url=http://dx.doi.org/10.1371/journal.pone.0021449