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Synthesis of IL-6 by hepatocytes is a normal response to common hepatic stimuli

Norris, CA and He, M and Kang, LI and Ding, MQ and Radder, JE and Haynes, MM and Yang, Y and Paranjpe, S and Bowen, WC and Orr, A and Michalopoulos, GK and Stolz, DB and Mars, WM (2014) Synthesis of IL-6 by hepatocytes is a normal response to common hepatic stimuli. PLoS ONE, 9 (4).

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Exogenous interleukin 6 (IL-6), synthesized at the initiation of the acute phase response, is considered responsible for signaling hepatocytes to produce acute phase proteins. It is widely posited that IL-6 is either delivered to the liver in an endocrine fashion from immune cells at the site of injury, or alternatively, in a paracrine manner by hepatic immune cells within the liver. A recent publication showed there was a muted IL-6 response in lipopolysaccharide (LPS)-injured mice when nuclear NFκB was specifically inactivated in the hepatocytes. This indicates hepatocellular signaling is also involved in regulating the acute phase production of IL-6. Herein, we present extensive in vitro and in vivo evidence that normal hepatocytes are directly induced to synthesize IL-6 mRNAs and protein by challenge with LPS, a bacterial hepatotoxin, and by HGF, an important regulator of hepatic homeostasis. As the IL-6 receptor is found on the hepatocyte, these results reveal that induction of the acute phase response can be regulated in an autocrine as well as endocrine/paracrine fashion. Further, herein we provide data indicating that following partial hepatectomy (PHx), HGF differentially regulates IL-6 production in hepatocytes (induces) versus immune cells (suppresses), signifying disparate regulation of the cell sources involved in IL-6 production is a biologically relevant mechanism that has previously been overlooked. These findings have wide ranging ramifications regarding how we currently interpret a variety of in vivo and in vitro biological models involving elements of IL-6 signaling and the hepatic acute phase response. © 2014 Norris et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Norris, CA
He, M
Kang, LI
Ding, MQdingm@pitt.eduDINGM
Radder, JEjor54@pitt.eduJOR54
Haynes, MMmmh51@pitt.eduMMH51
Yang, Y
Paranjpe, Sshirish@pitt.eduSHIRISH
Bowen, WCbowen@pitt.eduBOWEN
Orr, Aavo4@pitt.eduAVO4
Michalopoulos, GKmichal@pitt.eduMICHAL
Stolz, DBdonna.stolz@pitt.eduDSTOLZ
Mars, WMwmars@pitt.eduWMARS
ContributionContributors NameEmailPitt UsernameORCID
Date: 24 April 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0096053
Schools and Programs: School of Medicine > Cell Biology and Molecular Physiology
School of Medicine > Pathology
Refereed: Yes
Date Deposited: 23 Jun 2014 20:59
Last Modified: 02 Feb 2019 16:56


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