Decreased IL-10 expression in stefin B-deficient macrophages is regulated by the MAP kinase and STAT-3 signaling pathways

FEBS Lett. 2014 Mar 3;588(5):720-6. doi: 10.1016/j.febslet.2014.01.015. Epub 2014 Jan 23.


Innate immune responses are tightly regulated to avoid excessive activation and subsequent inflammatory damage to the host, and interleukin-10 (IL-10) plays a crucial role in preventing inflammation. Stefin B (cystatin B) is an endogenous inhibitor of cysteine proteinases. In stefin B-deficient bone marrow-derived macrophages (BMDMs), we detected an increase in the induction of the LPS-induced pro-inflammatory signal nitric oxide (NO) but decreased IL-10 expression. The phosphorylation of ERK and p38 MAP-kinases was significantly decreased in stefin B-deficient macrophages, as was STAT-3 phosphorylation. These findings show that stefin B influences the expression of anti-inflammatory IL-10 in response to the TLR4 agonist LPS.

Keywords: Cystatin; Interleukin-10; Lipopolysaccharide; MAP-kinase; Macrophage; Nitric oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cystatin B / deficiency*
  • Cystatin B / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System
  • Macrophage Activation
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Mice, Knockout
  • Nitric Oxide / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Transcriptional Activation / immunology


  • IL10 protein, mouse
  • Lipopolysaccharides
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Interleukin-10
  • Nitric Oxide
  • Interferon-gamma
  • Cystatin B
  • Extracellular Signal-Regulated MAP Kinases