RRC ID 62852
著者 Kanai R, Nakashima A, Doi S, Kimura T, Yoshida K, Maeda S, Ishiuchi N, Yamada Y, Ike T, Doi T, Kato Y, Masaki T.
タイトル Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis.
ジャーナル 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.
巻・号 11(1)
ページ 850
公開日 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
リソース情報
ヒト・動物細胞 THP-1(RCB1189)