3 years ago

Class IIa HDACs inhibitor TMP269 promotes M1 polarization of macrophages after spinal cord injury

Xiangbei Qi, Pengcheng Wang
Spinal cord injury (SCI) is a devastating disease insulting neurological system, and it could be further exacerbated by overwhelming inflammatory responses, where macrophages play a central role. Depending on their heterogeneous phenotypes, macrophages contribute intricately to SCI's pathological processes and functional recovery. Although stimuli like interferons and cytokines are known to regulate their phonotypical transition, it remains elusive which epigenetic programs macrophages engage to complete phenotype shift. We report here that, the treatment of TMP269, a highly-selective class IIa HDACs inhibitor, augments the production of pro-inflammatory cytokines in macrophages after SCI, meanwhile, TMP269 also promotes their M1 phenotype activation, which is independent of Th1 or Th2 cytokines. Moreover, TMP269 exacerbates tissue damage and impairs functional recovery after SCI. At last, the adoptive transfer of bone marrow-derived macrophages (BMDMs) overexpressing class IIa HDACs shows beneficial effects in inflammation resolution and functional recovery after SCI. Thus, activating the class IIa HDACs to harness the anti-inflammatory effects of macrophages may represent a potential target to treat SCI. This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcb.26446

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