Bone morphogenetic protein 6-induced interleukin-1β expression in macrophages requires PU.1/Smad1 interaction

Geun Taek Lee, Yeon Suk Jung, Jae Ho Lee, Wun Jae Kim, Isaac Kim

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Interleukin 1β (IL-1β) is a pro-inflammatory cytokine secreted by activated macrophages and monocytes. Previously, we have reported that bone morphogenetic protein-6 (BMP-6) induces inducible nitric oxide synthase (iNOS) expression via IL-1β in macrophages. In the present study, we demonstrate that BMP-6 increases IL-1β expression in macrophages via the receptors ALK3 and BMPRII as well as the downstream signaling protein Smad1. Surprisingly though, inhibition of the ERK and JNK non-Smad pathways also completely blocked the induction of IL-1β by BMP-6 in macrophages. Further analysis revealed that a physical interaction between the transcription factor PU.1 and Smad 1 is necessary for the upregulation of IL-1β expression by BMP-6 in macrophages. Taken together, these results demonstrate that BMP-6-induced IL-1β expression in macrophages is mediated via a cross-talk between the Smad and the non-Smad pathways through Smad1 and PU.1.

Original languageEnglish (US)
Pages (from-to)1540-1547
Number of pages8
JournalMolecular Immunology
Volume48
Issue number12-13
DOIs
StatePublished - Jul 2011

All Science Journal Classification (ASJC) codes

  • Immunology
  • Molecular Biology

Keywords

  • Bone morphogenetic protein-6
  • Cytokines
  • IL-1β
  • Macrophages
  • PU.1

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