A neuropeptide, Substance-P, directly induces tissue-repairing M2 likemacrophages by activating the PI3K/Akt/mTOR pathway even in the presenceof IFN gamma

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473765.do
DOI
10.1038/s41598-017-09639-7
Title
A neuropeptide, Substance-P, directly induces tissue-repairing M2 likemacrophages by activating the PI3K/Akt/mTOR pathway even in the presenceof IFN gamma
Description
This work was supported by grants NRF2012M3A9C6050499 andNRF2016M3A9B4917320 from the Korean Ministry of Science, ICT and FuturePlanning, and HI13C1479 from Korean Ministry of Health and Welfare toDr. YS Son.
abstract
Macrophage polarization plays an important role in tissue damage and repair. In this study, we show that Substance-P (SP) can directly induce M2 polarization of inflammatory macrophages. SP induced the differentiation of GM-CSF-differentiated pro-inflammatory macrophages into alternatively activated phagocytic M2 like macrophages (M2(SP)) through direct activation of the PI3K/Akt/mTOR/ S6kinase pathway and induction of Arginase-1, CD163, and CD206, all of which were nullified by pretreatment with the neurokinin-1 receptor (NK-1R) antagonist RP67580 and specific signaling pathway inhibitors. M2(SP) were distinct from IL-4/IL-13-induced M2a and IL-10-induced M2c subtypes; they did not show STAT activation and exhibited high phagocytic and endothelial adhesive activity. Furthermore, SP had a dominant effect on M2 polarization over Interferon gamma (IFN gamma), a potent M1-skewing cytokine, and effectively induced the M2 phenotype in monocytes and the human THP-1 cell line. Finally, adoptively transferred M2(SP) migrated to a spinal cord injury (SCI) lesion site and improved functional recovery. Collectively, our findings show that SP, a neuropeptide, plays a role as a novel cytokine by inducing tissue-repairing M2(SP) macrophages and thus may be developed for pharmacological intervention in diseases involving chronic inflammation and acute injury.
provenance
Made available in Cube on 2018-09-28T10:28:16Z (GMT). No. of bitstreams: 0
language
English
author
Lim, Ji Eun
Chung, Eunkyung
Son, Youngsook
accessioned
2018-09-28T10:28:16Z
available
2018-09-28T10:28:16Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473765.do
Funder
보건복지부
Funding Program
질환극복기술개발
Project ID
1465024760
Jurisdiction
Rep.of Korea
Project Name
The study for safety of Stem cell-stimulating factor and the establishment of the clinical manufacturing system
rights
openAccess
type
article


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