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Chemerin Isoform-Specific Effects on Hepatocyte Migration and Immune Cell Inflammation.

Susanne Feder1, Astrid Bruckmann2, Nichole McMullen3

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|October 2, 2020
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Summary

The longer chemerin isoforms, human chem-157 and murine chem-156, inhibit hepatocyte migration, potentially protecting against hepatocellular carcinoma (HCC) metastasis. Human chem-155 showed anti-inflammatory effects on immune cells.

Keywords:
CMKLR1GPR1Tango assayproliferation

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Area of Science:

  • Hepatology
  • Immunology
  • Molecular Biology

Background:

  • Chemerin isoforms, muChem-156 and muChem-155, are derived from murine chemerin, with muChem-156 known to protect against hepatocellular carcinoma (HCC).
  • The specific role of muChem-155 and the comparative effects of human and murine chemerin isoforms on liver cells remain largely unexplored.

Purpose of the Study:

  • To compare the effects of human (huChem-157, huChem-156) and murine (muChem-156, muChem-155) chemerin isoforms on hepatocyte proliferation, migration, and secretome.
  • To investigate the activation of chemerin receptors (CMKLR1, GPR1) by these isoforms in different cell lines.

Main Methods:

  • Overexpression of human and murine chemerin isoforms in human (HepG2, Huh7) and murine (Hepa1-6) hepatocyte cell lines.
  • Assays to measure cell proliferation, viability, migration, and receptor activation (CMKLR1, GPR1).
  • Analysis of cytokine profiles (IL-8, CCL20, osteopontin, CCL2) in conditioned media and their effects on peripheral blood mononuclear cells (PBMCs).

Main Results:

  • Both huChem-157 and muChem-156 significantly reduced migration in HepG2 and Hepa1-6 cells, suggesting a role in preventing HCC metastasis.
  • Chemerin isoforms activated CMKLR1 and GPR1 receptors, with varying potencies across human and murine systems.
  • Overexpression of chemerin variants did not affect hepatocyte proliferation or viability, nor did it alter key cytokines in hepatocytes.
  • Interestingly, the inactive human variant huChem-155 reduced CCL2 and IL-8 levels in PBMCs, indicating anti-inflammatory potential.

Conclusions:

  • Human chem-157 and murine chem-156 isoforms exhibit anti-migratory effects on hepatocytes, potentially contributing to HCC metastasis prevention.
  • Human chem-155 demonstrates anti-inflammatory properties by modulating cytokine release in immune cells.
  • These findings highlight distinct functional roles for different chemerin isoforms in liver health and inflammation.