Stimulation of Proliferation and Migration of Mouse Macrophages by Type B CpG-ODNs Is F-Spondin and IL-1Ra Dependent

Tai-An Chen; Chiao-Chun Liao; Yung-Chih Cheng; Yen-Po Chen; Yi-Fan Hsu; Chi-Ming Liang; Shu-Mei Liang

doi:10.1371/journal.pone.0128926

Stimulation of Proliferation and Migration of Mouse Macrophages by Type B CpG-ODNs Is F-Spondin and IL-1Ra Dependent

PLoS One. 2015 Jun 4;10(6):e0128926. doi: 10.1371/journal.pone.0128926. eCollection 2015.

Authors

Tai-An Chen¹, Chiao-Chun Liao², Yung-Chih Cheng¹, Yen-Po Chen¹, Yi-Fan Hsu¹, Chi-Ming Liang², Shu-Mei Liang³

Affiliations

¹ Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
² Genomics Research Center, Academia Sinica, Taipei, Taiwan.
³ Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Abstract

Macrophage proliferation and migration are important for many facets of immune response. Here we showed that stimulation of macrophages with type B CpG oligodeoxynucleotides (CpG-B ODNs) such as CpG-ODN 1668 increased the production of anti-inflammatory cytokine interleukin 1 receptor antagonist (IL-1Ra) in a TLR9- and MyD88-dependent manner. The CpG-B ODNs-induced IL-1Ra increased macrophage migration and promoted macrophage proliferation by down-regulating the expression of a cell cycle negative regulator, p27 to increase cell population in the S phase. The induction of IL-1Ra by CpG-B ODNs was F-spondin dependent. Knockdown of F-spondin and IL-1Ra decreased CpG-B ODNs-induced macrophage migration whereas overexpression of IL-1Ra increased migration of those cells. These findings demonstrated novel roles for F-spondin and IL-1Ra in CpG-B ODNs-mediated cell proliferation and migration of macrophages.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Movement / drug effects*
Cell Proliferation / drug effects
Extracellular Matrix Proteins / metabolism*
Gene Knockdown Techniques
Interleukin 1 Receptor Antagonist Protein / metabolism*
Macrophages / cytology*
Macrophages / drug effects
Macrophages / metabolism*
Mice
Mice, Inbred BALB C
Myeloid Differentiation Factor 88 / metabolism
Oligodeoxyribonucleotides / pharmacology*
RAW 264.7 Cells
S Phase / drug effects
Signal Transduction / drug effects
Toll-Like Receptor 9 / metabolism
Up-Regulation / drug effects

Substances

CPG-oligonucleotide
Extracellular Matrix Proteins
F-spondin protein, mouse
Interleukin 1 Receptor Antagonist Protein
Myeloid Differentiation Factor 88
Oligodeoxyribonucleotides
Toll-Like Receptor 9

Grants and funding

This project was funded by Academia Sinica, Program Project on Genomics and Proteomics (grant AS-94F-006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.