Autophagy is required for IL-2-mediated fibroblast growth

Rui Kang, Daolin Tang, Michael T. Lotze, Herbert J. Zeh

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Autophagy is an evolutionarily conserved pathway responsible for delivery of cytoplasmic material into the lysosomal degradation pathway to enable vesicular exocytosis. Interleukin (IL)-2 is produced by T-cells and its activity is important for immunoregulation. Fibroblasts are an immune competent cell type, playing a critical role in wound healing, chronic inflammation, and tumor development. Although autophagy plays an important role in each of these processes, whether it regulates IL-2 activity in fibroblasts is unknown. Here, we show that autophagy is required for IL-2-induced cell growth in fibroblasts. IL-2 significantly induced autophagy in mouse embryonic fibroblasts (MEFs) and primary lung fibroblasts. Autophagy inhibitors (e.g., 3-methylamphetamine and bafilomycin A1) or knockdown of ATG5 and beclin 1 blocked clinical grade IL-2-induced autophagy. Moreover, IL-2 induced HMGB1 cytoplasmic translocation in MEFs and promoted interaction between HMGB1 and beclin1, which is required for autophagy induction. Pharmacological and genetic inhibition of autophagy inhibited IL-2-induced cell proliferation and enhanced IL-2-induced apoptosis. These findings suggest that autophagy is an important pro-survival regulator for IL-2-induced cell growth in fibroblasts.

Original languageEnglish (US)
Pages (from-to)556-565
Number of pages10
JournalExperimental Cell Research
Volume319
Issue number4
DOIs
StatePublished - Feb 15 2013
Externally publishedYes

Keywords

  • Apoptosis
  • Autophagy
  • HMGB1
  • IL-2
  • Immunotherapy

ASJC Scopus subject areas

  • Cell Biology

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