Diesel Exhaust Particles Impair Therapeutic Effect of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis through ROS/ERK/cFos Signaling Pathway

Hyun Sung Park, Mi Kyung Oh, Joong Won Lee, Dong Hoon Chae, Hansol Joo, Ji Yeon Kang, Hye Bin An, Aaron Yu, Jae Han Park, Hee Min Yoo, Hyun Jun Jung, Uimook Choi, Ji Won Jung, In Sook Kim, Il Hoan Oh, Kyung Rok Yu

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objectives: Epidemiological investigations have shown positive correlations between increased diesel exhaust particles (DEP) in ambient air and adverse health outcomes. DEP are the major constituent of particulate atmospheric pollution and have been shown to induce proinflammatory responses both in the lung and systemically. Here, we report the effects of DEP exposure on the properties of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs), including stemness, regeneration, and immunomodulation. Methods and Results: Non-apoptotic concentrations of DEP (10 μg/ml) inhibited the migration and osteogenic differentiation capacity of WJ-MSCs. Gene expression profiling showed that DEP increased intracellular reactive oxygen species (ROS) and expression of pro-inflammatory and metabolic-process-related genes including cFos. Furthermore, WJ-MSCs cultured with DEP showed impaired suppression of T cell proliferation that was reversed by inhibition of ROS or knockdown of cFos. ERK inhibition assay revealed that DEP-induced ROS regulated cFos through activation of ERK but not NF-κB signaling. Overall, low concentrations of DEP (10 μg/ml) significantly suppressed the stemness and immunomodulatory properties of WJ-MSCs through ROS/ERK/cFos signaling pathways. Furthermore, WJ-MSCs cultured with DEP impaired the therapeutic effect of WJ-MSCs in experimental colitis mice, but was partly reversed by inhibition of ROS. Conclusions: Taken together, these results indicate that exposure to DEP enhances the expression of pro-inflammatory cytokines and immune responses through a mechanism involving the ROS/ERK/cFos pathway in WJ-MSCs, and that DEP-induced ROS damage impairs the therapeutic effect of WJ-MSCs in colitis. Our results suggest that modulation of ROS/ERK/cFos signaling pathways in WJ-MSCs might be a novel therapeutic strategy for DEP-induced diseases.

Original languageEnglish (US)
Pages (from-to)203-216
Number of pages14
JournalInternational Journal of Stem Cells
Volume15
Issue number2
DOIs
StatePublished - May 2022

Keywords

  • Cfos
  • Diesel exhaust particle
  • Erk
  • Immunomodulation
  • Mesenchymal stem cell
  • Oxidative stress

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology

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