Lipid IVa incompletely activates MyD88‐independent Toll‐like receptor 4 signaling in mouse macrophage cell lines

Abstract 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, E. 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 to 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 towards MyD88‐independent signaling of TLR4, in macrophage cell‐lines, despite having efficient activity in the MyD88‐dependent pathway. © 2013 Federation of European Mi...
Source: FEMS Immunology and Medical Microbiology - Category: Microbiology Authors: Tags: Research Paper Source Type: research