Cultured human liver fat-storing cells produce monocyte chemotactic protein-1 regulation by proinflammatory cytokines

Fabio Marra, Anthony J. Valante, Massimo Pinzani, Hanna E. Abboud

Research output: Contribution to journalArticle

175 Scopus citations

Abstract

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-1α (IL-1α) or interferon-γ (IFN-γ). Tumor necrosis factor-α (TNFα) also increased MCP-1 secretion, although to a lesser extent (1.6-fold). Northern blot analysis showed that IL-1α and IFN-γ strongly increase the levels of mRNA that encodes for MCP-1, whereas TNFα 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.

Original languageEnglish (US)
Pages (from-to)1674-1680
Number of pages7
JournalJournal of Clinical Investigation
Volume92
Issue number4
DOIs
StatePublished - 1993

Keywords

  • Interferon-γ
  • Interleukin-1α
  • Platelet-derived growth factor
  • Protein kinase C
  • Tumor necrosis factor α

ASJC Scopus subject areas

  • Medicine(all)

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