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Cultured Human Liver Fat-Storing Cells Produce Monocyte Chemotactic Protein-1. Regulation by Proinflammatory Cytokines
Open accessAbstract
Monocytes infiltrate the portal space during chronic liver inflammation. Monocyte chemotactic protein-1 (MCP-1) is a cytokine that induces monocyte chemotaxis and activation. We investigated if human liver fat-storing cells (FSC) secrete MCP-1, and the mechanisms that regulate MCP-1 production. Unstimulated FSC secrete MCP-1 as measured by radioimmunoassay as well as a chemotactic assay and express mRNA that encodes for this cytokine. A two- to threefold increase in MCP-1 secretion was observed when FSC were treated with either interleukin-1 alpha (IL-1 alpha) or interferon-gamma (IFN-gamma). Tumor necrosis factor-alpha (TNF alpha) also increased MCP-1 secretion, although to a lesser extent (1.6-fold). Northern blot analysis showed that IL-1 alpha and IFN-gamma strongly increase the levels of mRNA that encodes for MCP-1, whereas TNF alpha appears to be a weaker stimulus. Analysis of FSC-conditioned medium by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting revealed three bands of MCP-1 that most likely represent isoforms of different apparent molecular weights. Pretreatment of FSC with H-7, a protein kinase C inhibitor, blocked cytokine-induced increase in both MCP-1 gene expression and secretion. To determine the potential role of MCP-1 in vivo, we also analyzed normal and pathologic human liver tissue. Northern blot analysis showed that MCP-1 mRNA expression is more abundant in liver tissue obtained from patients with chronic active hepatitis compared with normal liver tissue. These studies indicate that MCP-1 secreted by FSC is stimulated by proinflammatory cytokines and that MCP-1 gene expression is upregulated in chronic inflammatory liver disease. MCP-1 released by FSC may participate in the recruitment and activation of monocytes at sites of liver injury.
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“Activated HSCs recruit immune cells by secreting numerous chemokines including monocyte chemoattractant protein-1 (MCP-1) (34), IL-8 (35), RANTES and CCR5 (36), and SDF-1/CXCL-12 (37) and express adhesion molecules, ICAM-1 and VCAM-1, that promote the infiltration of leukocytes and macrophages (38, 39).”
From Hepatic Stellate Cell-Immune Interactions in NASH (2022) · cites this paper as [34]
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Metadata
- Authors
- Marra, F., Valente, A. J., Pinzani, M., & Abboud, H. E.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- University of Florence (IT)
- Venue
- Journal of Clinical Investigation
- Published
- 1993-10-01
- Volume
- 92
- Issue
- 4
- Pages
- 1674-1680
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC288326
- OpenAlex
- W2062874643
- Cited by
- 197
- References
- 39
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 9 · 2014: 4 · 2013: 4 · 2012: 7
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- National Institutes of Health (5r01dk043988-09, 33665, 5p01hl026890-10)
- National Heart, Lung, and Blood Institute (HL-26890)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK43988, DK-33665)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- MCP-1, hepatocytes, inflammatory cytokines, interleukin-1 alpha, interferon-gamma, TNF-α, protein kinase C, chronic active hepatitis, monocyte recruitment, chronic liver inflammation, MCP-1 gene expression
- MeSH terms
- Cells, Cultured, Chemotactic Factors, Electrophoresis, Polyacrylamide Gel, Humans, Inflammation, Interferon-gamma, Interleukin-1, Isoquinolines, Liver, Molecular Weight, Piperazines, Platelet-Derived Growth Factor, Protein Kinase C, Radioimmunoassay, Recombinant Proteins, RNA, Messenger, Tumor Necrosis Factor-alpha, Blotting, Northern, Gene Expression, Cytokines, Adipocytes, Chemokine CCL2, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Culture Techniques
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