TIPE2 governs macrophage polarization via negative regulation of mTORC1

Jiang,Yuan; Li,Qiang; Zhang,Yuanyuan; Gao,Yuzhi; Jiang,Libing; Chen,Zhimin

doi:10.3892/mmr.2017.7991

TIPE2 governs macrophage polarization via negative regulation of mTORC1

Authors:
- Yuan Jiang
- Qiang Li
- Yuanyuan Zhang
- Yuzhi Gao
- Libing Jiang
- Zhimin Chen
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Affiliations: Department of Pulmonology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310051, P.R. China, Emergency Department, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: November 6, 2017 https://doi.org/10.3892/mmr.2017.7991
Pages: 952-960
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Macrophages can be polarized into the inflammatory M1 lineage or the immunomodulatory M2 lineage, depending on the differential tissue microenvironment signaling, specific pathogens or cytokine stimulation. Tumor necrosis factor α‑induced protein 8‑like protein 2 (TIPE2) has been demonstrated to negatively regulate inflammation by inhibiting the Toll‑like receptor (TLR) pathway. The present study utilized murine bone marrow derived macrophages (BMDMs) as the model of undifferentiated (M0) macrophages to study the roles of TIPE2 in the differential polarization status of BMDMs. It was observed that the expression levels of TIPE2 were diminished in M1 macrophages treated with lipopolysaccharide/interferon γ, and elevated in M2 macrophages treated with interleukin (IL)‑4. BMDMs with TIPE2 overexpression exhibited defective M1 polarization and enhanced responses to IL‑4 stimulation. TIPE2 impeded M1 polarization by interfering with mitogen‑activated protein kinase kinase kinase 7‑inhibitor of nuclear factor‑κB kinase subunit β and B cell receptor‑associated protein‑serine/threonine‑protein kinase mTOR complex 1 (mTORC1) activation. TIPE2 overexpression accelerated IL‑4 induced M2 polarization by dampening mTORC1 activation via the accelerated process of arginine to urea. Overall, these results define a key role for TIPE2 in macrophage polarization by impeding mTORC1 response.

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