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Cited by 156Liver physiology and pathologyCytokine Signaling Pathways and InteractionsNF-κB Signaling Pathways

Hepatocyte Growth Factor Modulates Interleukin-6 Production in Bone Marrow Derived Macrophages: Implications for Inflammatory Mediated Diseases

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Coudriet, Gina M., He, Jing, Trucco, Massimo, Mars, Wendy M., Piganelli, Jon D.·2010·PLoS ONE
DOI 10.1371/journal.pone.0015384PMC PMC2970559
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Abstract

The generation of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β fuel the acute phase response (APR). To maintain body homeostasis, the increase of inflammatory proteins is resolved by acute phase proteins via presently unknown mechanisms. Hepatocyte growth factor (HGF) is transcribed in response to IL-6. Since IL-6 production promotes the generation of HGF and induces the APR, we posited that accumulating HGF might be a likely candidate for quelling excess inflammation under non-pathological conditions. We sought to assess the role of HGF and how it influences the regulation of inflammation utilizing a well-defined model of inflammatory activation, lipopolysaccharide (LPS)-stimulation of bone marrow derived macrophages (BMM). BMM were isolated from C57BL6 mice and were stimulated with LPS in the presence or absence of HGF. When HGF was present, there was a decrease in production of the pro-inflammatory cytokine IL-6, along with an increase in the anti-inflammatory cytokine IL-10. Altered cytokine production correlated with an increase in phosphorylated GSK3β, increased retention of the phosphorylated NFκB p65 subunit in the cytoplasm, and an enhanced interaction between CBP and phospho-CREB. These changes were a direct result of signaling through the HGF receptor, MET, as effects were reversed in the presence of a selective inhibitor of MET (SU11274) or when using BMM from macrophage-specific conditional MET knockout mice. Combined, these data provide compelling evidence that under normal circumstances, HGF acts to suppress the inflammatory response.

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  • In cultured macrophages, HGF suppresses production of IL-6.

    “in cultured macrophages HGF suppresses production of IL-6”

    From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [10]

    The Results section ('HGF suppresses inflammation in bone marrow-derived macrophages') reports that HGF significantly suppressed IL-6 production in cultured, LPS-stimulated bone marrow-derived macrophages. The claim omits the LPS-stimulation condition and describes cultured macrophages more broadly. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • HGF suppresses LPS-induced production of IL-6 in cultured macrophages via the MET receptor.

    “As we have previously shown HGF suppresses LPS-induced production of IL-6 in cultured macrophages via the MET receptor [10]”

    From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [10]

  • Hepatocellular IL-6 induction in response to HGF is exactly the opposite of the effect of HGF on IL-6 in cultured macrophages.

    “hepatocellular IL-6 induction in response to HGF is exactly the opposite of what we recently observed with regard to HGF and IL-6 in cultured macrophages [10]”

    From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [10]

  • HGF can suppress IL-6 production in LPS-stimulated macrophages.

    “As we have previously shown that HGF can suppress IL-6 production in LPS-stimulated macrophages [10]”

    From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [10]

  • HGF suppresses IL-6 production in macrophages via signaling through the MET receptor.

    “In a recent publication we demonstrated that unlike what we now see with hepatocytes, HGF instead suppresses IL-6 production in macrophages via signaling through the MET receptor [10].”

    From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [10]

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Authors
Coudriet, G. M., He, J., Trucco, M., Mars, W. M., & Piganelli, J. D.
Affiliations
University of Pittsburgh (US)
Corresponding author
Piganelli, Jon D.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-11-02
Volume
5
Issue
11
Pages
e15384
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0015384
PMC
PMC2970559
OpenAlex
W2164624420
Cited by
155
References
39
Citations by year
2026: 2 · 2025: 6 · 2024: 17 · 2023: 6 · 2022: 13 · 2021: 14 · 2020: 12 · 2019: 9 · 2018: 10 · 2017: 8 · 2016: 17 · 2015: 6 · 2014: 11 · 2013: 9 · 2012: 10
FWCI
5.04
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • American Diabetes Association (CDA 7.07)
  • American Heart Association
  • University of Pittsburgh
  • Medical Center, University of Pittsburgh
  • Children's Hospital of Pittsburgh
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
hepatocyte growth factor, interleukin-6, bone marrow-derived macrophages, lipopolysaccharide stimulation, acute phase response, inflammation resolution, GSK3β, NF-κB p65, CREB, CBP, IL-10, anti-inflammatory cytokines
MeSH terms
Glycogen Synthase Kinase 3 beta, Animals, Bone Marrow Cells, Cells, Cultured, Dose-Response Relationship, Drug, Female, Indoles, Inflammation, Lipopolysaccharides, Macrophages, Male, Membrane Proteins, Mice, Inbred C57BL, Phosphoproteins, Phosphorylation, Piperazines, Protein Binding, Sulfonamides, Blotting, Western, Interleukin-6, Hepatocyte Growth Factor, Cyclic AMP Response Element-Binding Protein, Mice, Knockout, Proto-Oncogene Proteins c-met, Glycogen Synthase Kinase 3, Immunoprecipitation, Mice, Transcription Factor RelA, Mice, 129 Strain

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