Adipose-derived stem cells ameliorate colitis by suppression of inflammasome formation and regulation of M1-macrophage population through prostaglandin E2

Hong Jun Park, Jiye Kim, Fatema Tuj Saima, Ki Jong Rhee, Soonjae Hwang, Moon Young Kim, Soon Koo Baik, Young Woo Eom, Hyun Soo Kim

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23 Citations (Scopus)

Abstract

Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to intestinal microbes in an individual with a genetic predisposition. Therefore, alleviation of inflammation is very important to treat IBD. Mesenchymal stem cells (MSCs) have been highlighted as new candidates for treating autoimmune disease based on their immunomodulatory properties. In this study, we investigated the anti-inflammatory mechanism and therapeutic effects of adipose tissue-derived MSCs (ASCs) using THP-1 macrophages and dextran sodium sulfate (DSS)-induced mice with chronic colitis. LPS-treated THP-1 cells expressed mRNA of CD11b, an M1 macrophage marker, at day 2. However, THP-1 co-cultured with ASCs expressed mRNA of CD206, CD68, CCL18, legumain, and IL-10, markers of M2 macrophages. In THP-1 cells co-cultured with ASCs, precursor (pro)-IL-1β Cox-2, and NLRP3 increased dramatically compared to LPS-treated THP-1 cells. Secretion of IL-1β and IL-18 was significantly inhibited by ASCs, but PGE2 production was highly increased in co-culture conditions of THP-1 and ASCs. IL-18 secretion was inhibited by PGE2 treatment, and PGE2 inhibited inflammasome complex (ASC/Cas-1/NLRP3) formation in THP-1 cells. In the DSS-induced chronic colitis model, ASCs ameliorated colitis by decreasing the total number of macrophages and the M1 macrophage population. Our results suggest that ASCs can suppress the inflammatory response by controlling the macrophage population, and ASCs may be therapeutically useful for the treatment of IBD.

Original languageEnglish
Pages (from-to)988-995
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume498
Issue number4
DOIs
Publication statusPublished - 2018 Apr 15

Bibliographical note

Funding Information:
This work was supported by (1) a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute , funded by the Ministry of Health & Welfare, Republic of Korea ( HI17C1365 ), (2) a Basic Science Research program ( NRF-2017R1A2B4009199 and -2017R1C1B5017842 ), and (3) Small Grant for Exploratory Research (SGER) Program ( NRF-2017R1D1A1A02018088 and -2017R1D1A1A02019212 ) through the National Research Foundation of Korea funded by the Korean government (the Ministry of Education) .

Publisher Copyright:
© 2018 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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