Adipose-derived stem cells ameliorate colitis by suppression of inflammasome formation and regulation of M1-macrophage population through prostaglandin E2
| Autor: | Young Woo Eom, Soonjae Hwang, Jiye Kim, Ki Jong Rhee, Hyun Soo Kim, Soon Koo Baik, Fatema Tuj Saima, Hong Jun Park, Moon Young Kim |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Inflammasomes THP-1 Cells animal diseases Biophysics Cell Count Inflammation Biochemistry Inflammatory bowel disease Dinoprostone Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Macrophage Colitis Molecular Biology business.industry Macrophages Dextran Sulfate Mesenchymal stem cell CCL18 Mesenchymal Stem Cells hemic and immune systems Inflammasome Cell Biology medicine.disease Coculture Techniques 030104 developmental biology Adipose Tissue 030220 oncology & carcinogenesis Cancer research lipids (amino acids peptides and proteins) medicine.symptom business Inflammasome complex medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 498:988-995 |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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