Coudriet, GM and He, J and Trucco, M and Mars, WM and Piganelli, JD
(2010)
Hepatocyte growth factor modulates interleukin-6 production in bone marrow derived macrophages: Implications for inflammatory mediated diseases.
PLoS ONE, 5 (11).
Abstract
The generation of the pro-inflammatory cytokines IL-6, TNF-a, and IL-1b 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 GSK3b, increased retention of the phosphorylated NFkB 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. © 2010 Coudriet, et al.
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Details
| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
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| Contributors: |
| Contribution | Contributors Name | Email | Pitt Username | ORCID  |
|---|
| Editor | Zimmer, Jacques | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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| Date: |
18 November 2010 |
| Date Type: |
Publication |
| Journal or Publication Title: |
PLoS ONE |
| Volume: |
5 |
| Number: |
11 |
| DOI or Unique Handle: |
10.1371/journal.pone.0015384 |
| Refereed: |
Yes |
| MeSH Headings: |
Animals; Blotting, Western; Bone Marrow Cells--drug effects; Bone Marrow Cells--metabolism; Cells, Cultured; Cyclic AMP Response Element-Binding Protein--metabolism; Dose-Response Relationship, Drug; Female; Glycogen Synthase Kinase 3--metabolism; Hepatocyte Growth Factor--pharmacology; Immunoprecipitation; Indoles--pharmacology; Inflammation--metabolism; Interleukin-6--biosynthesis; Lipopolysaccharides--pharmacology; Macrophages--cytology; Macrophages--drug effects; Macrophages--metabolism; Male; Membrane Proteins--metabolism; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Phosphoproteins--metabolism; Phosphorylation--drug effects; Piperazines--pharmacology; Protein Binding--drug effects; Proto-Oncogene Proteins c-met--genetics; Proto-Oncogene Proteins c-met--metabolism; Sulfonamides--pharmacology; Transcription Factor RelA--metabolism |
| Other ID: |
NLM PMC2970559 |
| PubMed Central ID: |
PMC2970559 |
| PubMed ID: |
21072211 |
| Date Deposited: |
22 Aug 2012 21:56 |
| Last Modified: |
04 Feb 2019 15:58 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/13564 |
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