Lipopolysaccharides can protect mesenchymal stem cells (MSCs) from oxidative stress-induced apoptosis and enhance proliferation of MSCs via Toll-like receptor(TLR)-4 and PI3K/Akt.
Apoptosis of implanted mesenchymal stem cells (MSCs) limits the efficiency of MSC therapy. Recent studies showed the ligands of Toll-like receptors (TLRs) could control the function of these cells. We have investigated the effect of lipopolysaccharides (LPS), a ligand of TLR4, on the survival of MSCs and explored the roles of TLR4 and PI3K/Akt. H(2)O(2)/serum deprivation(H(2)O(2)/SD) induced apoptosis of MSCs but LPS-preconditioning (1.0microg/ml) protected MSCs from H(2)O(2)/SD-induced apoptosis and promoted their proliferation. Western blotting showed that 1.0microg/ml LPS enhanced phosphorylation of both Akt at Ser 473 and nuclear factor-kappa B (NF-kappaB) p65 at Ser 536. However, the protective effects of LPS on survival were not observed in TLR4(lps-del) MSCs. The results suggest appropriate treatments with LPS can protect MSCs from oxidative stress-induced apoptosis and improve the survival of MSCs via the TLR4 and PI3K/Akt pathway.
Wang
Zhao-jun
ZJ
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
Zhang
Fu-min
FM
Wang
Lian-sheng
LS
Yao
Yong-wei
YW
Zhao
Qiang
Q
Gao
Xiang
X
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism
D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt