The manuscript contains interesting novel observation that lipid IVa preferentially stimulates MyD88-associated NFkB signaling in mouse macrophage cell-lines. This information will be useful to those who investigate mechanisms of differential signaling adapter usage by the TLR4/MD2 LPS receptor.
Lipid IVa incompletely activates MyD88-independent Toll-like receptor 4 signaling in mouse macrophage cell lines
Version of Record online: 4 MAR 2013
© 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved
Pathogens and Disease
Volume 67, Issue 3, pages 199–205, April 2013
How to Cite
Ogura, N., Muroi, M., Sugiura, Y. and Tanamoto, K.-i. (2013), Lipid IVa incompletely activates MyD88-independent Toll-like receptor 4 signaling in mouse macrophage cell lines. Pathogens and Disease, 67: 199–205. doi: 10.1111/2049-632X.12031
- Issue online: 8 APR 2013
- Version of Record online: 4 MAR 2013
- Accepted manuscript online: 12 FEB 2013 07:45AM EST
- Manuscript Accepted: 31 JAN 2013
- Manuscript Revised: 29 JAN 2013
- Manuscript Received: 3 DEC 2012
- innate immunity;
We investigated the difference in the effect of synthetic lipid A compounds on MyD88-dependent and -independent Toll-like receptor 4 (TLR4) signaling in mouse macrophage cells. At higher concentrations, Escherichia coli-type hexa-acylated lipid A 506, Salmonella-type hepta-acylated lipid A 516, the lipid A precursor lipid IVa and monophosphoryl lipid A induced similar levels of production of the MyD88-dependent cytokine IL-1β although their potencies varied, whereas the maximum production of the MyD88-independent cytokine RANTES induced by lipid IVa was less than 50% that of other lipid A compounds. A maximum level of NF-κB activation, which is involved in IL-1β gene transcription, was also induced to a similar level by these four lipid A compounds, while the maximum level of IFN-β promoter activity induced during MyD88-independent signaling was also less than 50% for lipid IVa stimulation compared with other lipid A compounds. Early IκBα phosphorylation activated by MyD88-dependent signaling was similarly induced by 506 and lipid IVa, whereas lipid IVa barely stimulated the phosphorylation of IRF3, a MyD88-independent transcription factor, although efficient phosphorylation was observed with 506 stimulation. These results indicate that lipid IVa has limited activity toward MyD88-independent signaling of TLR4, in macrophage cell lines, despite having efficient activity in the MyD88-dependent pathway.