Modulation of murine macrophage TLR7/8-mediated cytokine expression by mesenchymal stem cell-conditioned medium

Takahiro Asami, Makoto Ishii, Hideki Fujii, Ho Namkoong, Sadatomo Tasaka, Kenichi Matsushita, Ken Ishii, Kazuma Yagi, Hiroshi Fujiwara, Yohei Funatsu, Naoki Hasegawa, Tomoko Betsuyaku

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Abstract

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 E(PGE secreted by the MSCs. PGEenhanced extracellular signal-related kinase (ERK) signaling and suppressed nuclear factor-B (NF-B) signaling. Enhanced ERK signaling contributed to enhanced IL-10 production, and suppression of NF-B 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.

Original languageEnglish
Article number264260
JournalMediators of Inflammation
Volume2013
DOIs
Publication statusPublished - 2013 Oct 21

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ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Asami, T., Ishii, M., Fujii, H., Namkoong, H., Tasaka, S., Matsushita, K., Ishii, K., Yagi, K., Fujiwara, H., Funatsu, Y., Hasegawa, N., & Betsuyaku, T. (2013). Modulation of murine macrophage TLR7/8-mediated cytokine expression by mesenchymal stem cell-conditioned medium. Mediators of Inflammation, 2013, [264260]. https://doi.org/10.1155/2013/264260