Reactive oxygen species regulate M-CSF-induced monocyte/macrophage proliferation through SHP1 oxidation

Han Kyoung Choi, Tae Hee Kim, Gil Ja Jhon, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Macrophage colony-stimulating factor (M-CSF) stimulation results in the production of reactive oxygen species (ROS) that participate in the proliferation of monocyte/macrophage. However, the molecular mechanisms whereby ROS modulate the signaling processes of M-CSF remain poorly defined. We report here that the redox-sensitive Src homology region 2 domain-containing phosphatase 1 (SHP1) is a critical regulator of M-CSF-mediated signaling in bone marrow monocyte/macrophage lineage cells (BMMs). Application of diphenylene iodonium (DPI) inhibited the responses of BMMs to M-CSF, including ROS production, cell proliferation, and phosphorylation of c-Fms as well as Akt kinase, but not of MAP kinases such as ERK, p38, and JNK. Dysregulation of SHP1 by overexpression or RNA interference in BMMs showed that SHP1 specifically regulates PI3 kinase (PI3K)/Akt signaling, but not MAP kinases in a redox-dependent manner, thereby regulating proliferation of BMMs through cyclins D1 and D2. These findings demonstrate that M-CSF-mediated ROS generation leads to SHP1 oxidation, which promotes cell proliferation through the PI3K/Akt-dependent signaling pathway.

Original languageEnglish
Pages (from-to)1633-1639
Number of pages7
JournalCellular Signalling
Volume23
Issue number10
DOIs
StatePublished - Oct 2011

Bibliographical note

Funding Information:
We thank T. Kitamura for PLAT-E cells and K. Mizuno for pSPORT6-SHP1. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MEST) ( R0A-2008-000-20001-0 ; R31-2008-000-10010-0 ; No. 2011–0006244 ; No. 2010–0020577 ). H.C. was supported by the second stage of the Brain Korea 21 Project.

Keywords

  • M-CSF
  • Monocyte/macrophage
  • Oxidation
  • PI3K/Akt signaling
  • Proliferation
  • SHP1

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