RRC ID |
62852
|
Author |
Kanai R, Nakashima A, Doi S, Kimura T, Yoshida K, Maeda S, Ishiuchi N, Yamada Y, Ike T, Doi T, Kato Y, Masaki T.
|
Title |
Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis.
|
Journal |
Sci Rep
|
Abstract |
Mesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes require a substantial period of time, leading to a delayed onset of MSCs' therapeutic effects. In this study, we investigated whether pretreatment with IFN-γ could potentiate the anti-fibrotic ability of MSCs in rats with ischemia-reperfusion injury (IRI) and unilateral ureter obstruction. Administration of MSCs treated with IFN-γ strongly reduced infiltration of inflammatory cells and ameliorated interstitial fibrosis compared with control MSCs without IFN-γ treatment. In addition, conditioned medium obtained from IFN-γ-treated MSCs decreased fibrotic changes in cultured cells induced by transforming growth factor-β1 more efficiently than that from control MSCs. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 in conditioned medium obtained from IFN-γ-treated MSCs induced polarization of immunosuppressive CD163 and CD206-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ. Administration of MSCs treated with IFN-γ might represent a promising therapy to prevent the progression of renal fibrosis.
|
Volume |
11(1)
|
Pages |
850
|
Published |
2021-1-13
|
DOI |
10.1038/s41598-020-79664-6
|
PII |
10.1038/s41598-020-79664-6
|
PMID |
33441701
|
PMC |
PMC7807061
|
MeSH |
Animals
Antigens, CD / metabolism
Antigens, Differentiation, Myelomonocytic / metabolism
Cells, Cultured
Culture Media, Conditioned
Dinoprostone / metabolism
Fibrosis / therapy
Interferon-gamma / pharmacology*
Kidney / pathology
Kidney Diseases / drug therapy
Kidney Diseases / therapy*
Killer Cells, Natural / metabolism
Macrophages / metabolism
Male
Mesenchymal Stem Cell Transplantation / methods*
Mesenchymal Stem Cells / cytology*
Rats
Rats, Sprague-Dawley
Receptors, Cell Surface / metabolism
Reperfusion Injury / physiopathology
Reperfusion Injury / therapy
Ureteral Obstruction / physiopathology
Ureteral Obstruction / therapy
|
IF |
3.998
|
Resource |
Human and Animal Cells |
THP-1(RCB1189) |