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PRSS14/Epithin is induced in macrophages by the IFN-γ/JAK/STAT pathway and mediates transendothelial migration

Deokjae Lee1, Hyo Seon Lee, Soo Jung Yang

  • 1Department of Biological Sciences, Inha University, Yonghyun-dong, Incheon 402-751, Republic of Korea.

Biochemical and Biophysical Research Communications
|February 8, 2011
PubMed

Insights

PRSS14/Epithin is expressed in macrophages upon IFN-γ activation, regulating their migration. This finding suggests a role for PRSS14/Epithin in inflammatory responses and cancer metastasis.

Area of Science:

  • Cell Biology
  • Immunology
  • Protease Research

Background:

  • PRSS14/Epithin (matriptase/ST14), a type II transmembrane serine protease, is known for its roles in epithelial barrier function and cancer progression.
  • It is typically found in epithelial cells and associated with epithelial cancers.

Purpose of the Study:

  • To investigate the expression and function of PRSS14/Epithin in macrophages.
  • To determine the regulatory mechanisms of PRSS14/Epithin expression in macrophages and its role in macrophage migration.

Main Methods:

  • Analysis of PRSS14/Epithin expression in macrophage cell lines and primary macrophages stimulated with various cytokines (IFN-γ, TNF-α, TGF-β).
  • Investigation of the signaling pathways involved in PRSS14/Epithin induction using JAK pathway inhibitors and chromatin immunoprecipitation (ChIP) to identify STAT1 binding sites.
  • Assessment of macrophage transendothelial migration using PRSS14/Epithin knockdown cells.

Main Results:

  • PRSS14/Epithin is expressed in macrophages upon activation by IFN-γ, but not TNF-α or TGF-β.
  • IFN-γ-induced expression is regulated by JAK/STAT1 signaling and sustained over several days.
  • PRSS14/Epithin is crucial for IFN-γ-enhanced macrophage transendothelial migration, independent of other surface markers like ICAM1, CD80, and CD40.

Conclusions:

  • PRSS14/Epithin is induced in activated macrophages and plays a significant role in their transendothelial migration.
  • This function in macrophages suggests a potential role in inflammatory processes and parallels its known function in cancer metastasis.

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