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Macrophage responses to interferon-gamma are dependent on cystatin C levels

Katarina H Frendéus1, Hanna Wallin, Sabina Janciauskiene

  • 1Department of Laboratory Medicine, Division of Clinical Chemistry and Pharmacology, Lund University, University Hospital, SE-221 85 Lund, Sweden. Katarina.Hakansson@med.lu.se

The International Journal of Biochemistry & Cell Biology
|May 19, 2009
PubMed

Insights

Cystatin C influences macrophage inflammatory responses. Lowering cystatin C reduces pro-inflammatory signals like TNF-alpha, while increasing anti-inflammatory IL-10, suggesting cystatin C is an immunomodulatory molecule.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • Interferon-gamma (IFN-gamma) down-regulates cystatin C secretion in macrophages.
  • Investigating the impact of cystatin C levels on macrophage-mediated inflammatory responses is crucial.

Purpose of the Study:

  • To elucidate the effects of cystatin C on macrophage inflammatory responses.
  • To determine if altered cystatin C expression impacts IFN-gamma-induced inflammatory pathways.

Main Methods:

  • Comparison of IFN-gamma effects on macrophages from wild-type (cysC(+/+)) and cystatin C knockout (cysC(-/-)) mice.
  • Analysis of cytokine expression (IL-10, TNF-alpha), NF-kappaB activation, and nitric oxide production.
  • Assessment of gene and protein expression levels.

Main Results:

  • IFN-gamma-primed cysC(-/-) macrophages showed higher IL-10 and lower TNF-alpha expression, with reduced NF-kappaB p65 activation compared to cysC(+/+) cells.
  • Exogenous cystatin C enhanced NF-kappaB p65 activation, iNOS, nitric oxide, and TNF-alpha in cysC(-/-) macrophages, indicating a pro-inflammatory effect.
  • Exogenous cystatin C down-regulated IFN-gamma-induced IL-10 mRNA expression in cysC(-/-) macrophages.

Conclusions:

  • Cystatin C levels modulate macrophage responses to IFN-gamma.
  • IFN-gamma down-regulates cystatin C, leading to suppressed inflammation with increased IL-10 and decreased TNF-alpha and NF-kappaB.
  • Cystatin C acts as an immunomodulatory molecule by influencing inflammatory signaling pathways.

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