Open AccessLipid IVa incompletely activates MyD88‐independent Toll‐like receptor 4 signaling in mouse macrophage cell lines
Author(s) -
Ogura Norihiko,
Muroi Masashi,
Sugiura Yuka,
Tanamoto Kenichi
Publication year - 2013
Publication title -
pathogens and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.983
H-Index - 105
ISSN - 2049-632X
DOI - 10.1111/2049-632x.12031
Subject(s) - lipid a , toll like receptor , phosphorylation , signal transduction , tlr4 , biology , lipid signaling , lipid metabolism , receptor , transcription factor , cytokine , irf3 , microbiology and biotechnology , biochemistry , lipopolysaccharide , chemistry , innate immune system , immunology , gene
We investigated the difference in the effect of synthetic lipid A compounds on MyD88‐dependent and ‐independent Toll‐like receptor 4 ( TLR 4) 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.