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Expression level of human TLR4 rather than sequence is the key determinant of LPS responsiveness.

ABSTRACT: To address the role of Toll-like receptor 4 (TLR4) single nucleotide polymorphisms (SNP) in lipopolysaccharide (LPS) recognition, we generated mice that differed only in the sequence of TLR4. We used a bacterial artificial chromosome (BAC) transgenic approach and TLR4/MD-2 knockout mice to specifically examine the role of human TLR4 variants in recognition of LPS. Using in vitro and in vivo assays we found that the expression level rather than the sequence of TLR4 played a larger role in recognition of LPS, especially hypoacylated LPS.

SUBMITTER: Hajjar AM 

PROVIDER: S-EPMC5636155 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Expression level of human TLR4 rather than sequence is the key determinant of LPS responsiveness.

Hajjar Adeline M AM   Ernst Robert K RK   Yi Jaehun J   Yam Cathy S CS   Miller Samuel I SI  

PloS one 20171011 10

To address the role of Toll-like receptor 4 (TLR4) single nucleotide polymorphisms (SNP) in lipopolysaccharide (LPS) recognition, we generated mice that differed only in the sequence of TLR4. We used a bacterial artificial chromosome (BAC) transgenic approach and TLR4/MD-2 knockout mice to specifically examine the role of human TLR4 variants in recognition of LPS. Using in vitro and in vivo assays we found that the expression level rather than the sequence of TLR4 played a larger role in recogni  ...[more]

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