A novel anti-apoptotic role for apolipoprotein L2 in IFN-γ-induced cytotoxicity in human bronchial epithelial cells

J Cell Physiol. 2011 Feb;226(2):397-406. doi: 10.1002/jcp.22345.


Airway epithelium functions not only as a physical barrier, but also a regulator of lung inflammation. IFN-γ plays a critical role in airway inflammation associated with respiratory viral infection. We investigated differential protein profiling in IFN-γ-stimulated normal human bronchial epithelial cells (HBEC) using a 2-dimensional gel electrophoresis followed by MALDI-TOF-MS/MS. IFN-γ markedly stimulated apolipoprotein L2 (ApoL2) protein expression in normal HBEC. ApoL2 mRNA expression was also elevated in normal human lung fibroblasts and smooth muscle cells stimulated with IFN-γ, in lung tissues from an IFN-γ-predominant influenza A virus-infected mouse lung injury model, and in cancer lung tissues from human patients. Normal HBEC showed strong resistance to IFN-γ-induced cytotoxicity. ApoL2 knockdown by siRNA promoted IFN-γ-induced cytotoxicity as revealed by a significant drop in cell viability using MTT and CyQUANT NF cell proliferation assays, and a marked increase in hypodiploid sub-G1 cell population in cell cycle analysis. Furthermore, depletion of ApoL2 facilitated IFN-γ-induced membrane damage and chromatin condensation as observed in Hoechst and propidium iodide-double staining and in transmission electron microscopy, and DNA fragmentation using a DNA laddering assay, in a caspase-dependent manner. Our results reveal a novel function for ApoL2 in conferring anti-apoptotic ability of human bronchial epithelium to the cytotoxic effects of IFN-γ, in maintaining airway epithelial layer integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins / genetics
  • Apolipoproteins / metabolism*
  • Apolipoproteins L
  • Apoptosis / drug effects*
  • Bronchi / cytology*
  • Cells, Cultured
  • DNA Fragmentation
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / pathology*
  • Humans
  • Interferon-gamma / pharmacology*
  • Lipoproteins, HDL / genetics
  • Lipoproteins, HDL / metabolism*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mass Spectrometry
  • Mice
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Respiratory Mucosa / cytology*


  • APOL2 protein, human
  • Apolipoproteins
  • Apolipoproteins L
  • Lipoproteins, HDL
  • Protein Isoforms
  • RNA, Small Interfering
  • Interferon-gamma