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).
Abstract
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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Details
Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
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Norris, CA | | | | He, M | | | | Kang, LI | | | | Ding, MQ | dingm@pitt.edu | DINGM | | Radder, JE | jor54@pitt.edu | JOR54 | | Haynes, MM | mmh51@pitt.edu | MMH51 | | Yang, Y | | | | Paranjpe, S | shirish@pitt.edu | SHIRISH | | Bowen, WC | bowen@pitt.edu | BOWEN | | Orr, A | avo4@pitt.edu | AVO4 | | Michalopoulos, GK | michal@pitt.edu | MICHAL | | Stolz, DB | donna.stolz@pitt.edu | DSTOLZ | | Mars, WM | wmars@pitt.edu | WMARS | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID |
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Editor | Rénia, Laurent | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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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 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/21999 |
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