TLR3-/4-Priming Differentially Promotes Ca2+ Signaling and Cytokine Expression and Ca2+ -Dependently Augments Cytokine Release in hMSCs
- Title
- TLR3-/4-Priming Differentially Promotes Ca2+ Signaling and Cytokine Expression and Ca2+ -Dependently Augments Cytokine Release in hMSCs
- Author
- 이영식
- Keywords
- MESENCHYMAL STEM-CELLS; TOLL-LIKE RECEPTORS; INNATE IMMUNITY; FUNCTIONAL EXPRESSION; CALCIUM-CHANNELS; STROMAL CELLS; MODULATION; APOPTOSIS; ENTRY; LIPOPOLYSACCHARIDE
- Issue Date
- 2016-03
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v. 6, Article no. 23103
- Abstract
- In human mesenchymal stem cells (hMSCs), toll-like receptor 3 (TLR3) and TLR4 act as key players in the tissue repair process by recognizing their ligands and stimulating downstream processes including cytokine release. The mechanisms of TLR3-and TLR4-mediated cytokine releases from hMSCs remain uncertain. Here, we show that exposure to the TLR3 agonist polyinosinic-polycytidylic acid (poly(I:C)) or incubation with the TLR4 agonist lipopolysaccharide (LPS) increased the mRNA expression levels of TLR3, TLR4 and cytokines in hMSCs. Poly(I:C) exposure rather than LPS incubation not only elevated inositol 1,4,5-triphosphate receptor (IP3R) expression and IP3R-mediated Ca2+ release, but also promoted Orai and STIM expression as well as store-operated Ca2+ entry into hMSCs. In addition, we also observed that 21 Ca2+ signaling genes were significantly up-regulated in response to TLR3 priming of hMSCs by RNA sequencing analysis. Both poly(I: C) and LPS exposure enhanced cytokine release from hMSCs. The enhanced cytokine release vanished upon siRNA knockdown and chelation of intracellular Ca2+. These data demonstrate that TLR3-and TLR4-priming differentially enhance Ca2+ signaling and cytokine expression, and Ca2+ -dependently potentiates cytokine release in hMSCs.
- URI
- https://www.nature.com/articles/srep23103http://hdl.handle.net/20.500.11754/65535
- ISSN
- 2045-2322
- DOI
- 10.1038/srep23103
- Appears in Collections:
- COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
- Files in This Item:
There are no files associated with this item.
- Export
- RIS (EndNote)
- XLS (Excel)
- XML