Toll-like receptor 2 mediates proliferation, survival, NF-kappaB translocation, and cytokine mRNA expression in LIF-maintained mouse embryonic stem cells.

Stem Cells and Development
Tammi TaylorHal E Broxmeyer

Abstract

Toll-like receptor (TLR) activation is important in immune responses and in differentiation of hematopoietic stem cells. We detected mRNA expression of TLRs 1, 2, 3, 5, and 6, but not TLRs 4, 7, 8, and 9 in murine (m)ESC line E14, and noted high cell surface protein expression of TLR2, but not TLR4, for mESC lines R1, CGR8, and E14. ESC lines were cultured in the presence of leukemia inhibitory factor (LIF). Pam(3)Cys enhanced proliferation and survival of the 3 ESC lines. In contrast, lipopolysaccharide (LPS) decreased proliferation and survival. Pam(3)Cys and LPS effects on proliferation and survival were blocked by antibody to TLR2, suggesting that effects of both Pam(3)Cys and LPS on these mESC lines were likely mediated through TLR2. E14 ESC line expressed MyD88. Pam(3)Cys stimulation of E14 ESCs was associated with induced NF-kappaB translocation, enhanced phosphorylation of IKK-alpha/beta, and enhanced mRNA, but not protein, expression of tumor necrosis factor-alpha, interferon-gamma, and IL-6. TLR2 activation by Pam(3)Cys or inhibition by LPS was not associated with changes in morphology or expression of alkaline phosphatase, Oct4, SSEA1, KLF4, or Sox2, markers of undifferentiated mESCs. Our studies identify TLR2 as pre...Continue Reading

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Citations

Feb 11, 2012·Critical Reviews in Immunology·Uma Nagarajan
Oct 12, 2013·Journal of Bioscience and Bioengineering·Hiroaki AikawaYoh-ichi Tagawa
Mar 11, 2015·American Journal of Respiratory Cell and Molecular Biology·Janine ZahltenStefan Hippenstiel
Jan 29, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·William D'AngeloYan-Lin Guo
Aug 24, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Laura ContiFederica Cavallo
Jun 27, 2019·BioMed Research International·D M Abarca-MerlinL Alvarez-Arellano

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Methods Mentioned

BETA
electrophoresis
PCR
enzyme-linked immunosorbent assay
flow cytometry
Protein Assay
X-ray
ELISA
nuclear translocation

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