Modulation of Murine Macrophage TLR7/8-Mediated Cytokine Expression by Mesenchymal Stem Cell-Conditioned Medium
Increasing evidence suggests that mesenchymal stem cells (MSCs) play anti-inflammatory roles during innate immune responses. However, little is known about the effect of MSCs or their secretions on the ligand response of Toll-like receptor (TLR) 7 and TLR8, receptors that recognize viral single-stra...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/264260 |
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| _version_ | 1850222896260055040 |
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| author | Takahiro Asami Makoto Ishii Hideki Fujii Ho Namkoong Sadatomo Tasaka Kenichi Matsushita Ken Ishii Kazuma Yagi Hiroshi Fujiwara Yohei Funatsu Naoki Hasegawa Tomoko Betsuyaku |
| author_facet | Takahiro Asami Makoto Ishii Hideki Fujii Ho Namkoong Sadatomo Tasaka Kenichi Matsushita Ken Ishii Kazuma Yagi Hiroshi Fujiwara Yohei Funatsu Naoki Hasegawa Tomoko Betsuyaku |
| author_sort | Takahiro Asami |
| collection | DOAJ |
| description | Increasing evidence suggests that mesenchymal stem cells (MSCs) play anti-inflammatory roles during innate immune responses. However, little is known about the effect of MSCs or their secretions on the ligand response of Toll-like receptor (TLR) 7 and TLR8, receptors that recognize viral single-stranded RNA (ssRNA). Macrophages play a critical role in the innate immune response to ssRNA virus infection; therefore, we investigated the effect of MSC-conditioned medium on cytokine expression in macrophages following stimulation with TLR7/8 ligands. After stimulation with TLR7/8 ligand, bone marrow-derived macrophages cultured with MSCs or in MSC-conditioned medium expressed lower levels of tumor necrosis factor (TNF) α and interleukin (IL) 6 and higher levels of IL-10 compared to macrophages cultured without MSCs or in control medium, respectively. The modulations of cytokine expression were associated with prostaglandin E2 (PGE2) secreted by the MSCs. PGE2 enhanced extracellular signal-related kinase (ERK) signaling and suppressed nuclear factor-κB (NF-κB) signaling. Enhanced ERK signaling contributed to enhanced IL-10 production, and suppression of NF-κB signaling contributed to the low production of TNF-α. Collectively, these results indicate that MSCs and MSC-conditioned medium modulate the cytokine expression profile in macrophages following TLR7/8-mediated stimulation, which suggests that MSCs play an immunomodulatory role during ssRNA virus infection. |
| format | Article |
| id | doaj-art-6bc8bdbec7c04b92bafb94ad7377803e |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-6bc8bdbec7c04b92bafb94ad7377803e2025-08-20T02:06:08ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/264260264260Modulation of Murine Macrophage TLR7/8-Mediated Cytokine Expression by Mesenchymal Stem Cell-Conditioned MediumTakahiro Asami0Makoto Ishii1Hideki Fujii2Ho Namkoong3Sadatomo Tasaka4Kenichi Matsushita5Ken Ishii6Kazuma Yagi7Hiroshi Fujiwara8Yohei Funatsu9Naoki Hasegawa10Tomoko Betsuyaku11Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanSecond Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, JapanDepartment of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanCenter for Infection Disease and Infection Control, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanCenter for Infection Disease and Infection Control, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanIncreasing evidence suggests that mesenchymal stem cells (MSCs) play anti-inflammatory roles during innate immune responses. However, little is known about the effect of MSCs or their secretions on the ligand response of Toll-like receptor (TLR) 7 and TLR8, receptors that recognize viral single-stranded RNA (ssRNA). Macrophages play a critical role in the innate immune response to ssRNA virus infection; therefore, we investigated the effect of MSC-conditioned medium on cytokine expression in macrophages following stimulation with TLR7/8 ligands. After stimulation with TLR7/8 ligand, bone marrow-derived macrophages cultured with MSCs or in MSC-conditioned medium expressed lower levels of tumor necrosis factor (TNF) α and interleukin (IL) 6 and higher levels of IL-10 compared to macrophages cultured without MSCs or in control medium, respectively. The modulations of cytokine expression were associated with prostaglandin E2 (PGE2) secreted by the MSCs. PGE2 enhanced extracellular signal-related kinase (ERK) signaling and suppressed nuclear factor-κB (NF-κB) signaling. Enhanced ERK signaling contributed to enhanced IL-10 production, and suppression of NF-κB signaling contributed to the low production of TNF-α. Collectively, these results indicate that MSCs and MSC-conditioned medium modulate the cytokine expression profile in macrophages following TLR7/8-mediated stimulation, which suggests that MSCs play an immunomodulatory role during ssRNA virus infection.http://dx.doi.org/10.1155/2013/264260 |
| spellingShingle | Takahiro Asami Makoto Ishii Hideki Fujii Ho Namkoong Sadatomo Tasaka Kenichi Matsushita Ken Ishii Kazuma Yagi Hiroshi Fujiwara Yohei Funatsu Naoki Hasegawa Tomoko Betsuyaku Modulation of Murine Macrophage TLR7/8-Mediated Cytokine Expression by Mesenchymal Stem Cell-Conditioned Medium Mediators of Inflammation |
| title | Modulation of Murine Macrophage TLR7/8-Mediated Cytokine Expression by Mesenchymal Stem Cell-Conditioned Medium |
| title_full | Modulation of Murine Macrophage TLR7/8-Mediated Cytokine Expression by Mesenchymal Stem Cell-Conditioned Medium |
| title_fullStr | Modulation of Murine Macrophage TLR7/8-Mediated Cytokine Expression by Mesenchymal Stem Cell-Conditioned Medium |
| title_full_unstemmed | Modulation of Murine Macrophage TLR7/8-Mediated Cytokine Expression by Mesenchymal Stem Cell-Conditioned Medium |
| title_short | Modulation of Murine Macrophage TLR7/8-Mediated Cytokine Expression by Mesenchymal Stem Cell-Conditioned Medium |
| title_sort | modulation of murine macrophage tlr7 8 mediated cytokine expression by mesenchymal stem cell conditioned medium |
| url | http://dx.doi.org/10.1155/2013/264260 |
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