Identification of a novel isoform of MD-2 that downregulates lipopolysaccharide signaling

Biochemical and Biophysical Research Communications
Shoichiro OhtaMasao Kimoto

Abstract

MD-2 is an association molecule of Toll-like receptor 4 and is indispensable for the recognition of lipopolysaccharide. Here we report the identification of mRNA for an alternatively spliced form of MD-2, named MD-2B, which lacks the first 54 bases of exon 3. When overexpressed with MD-2, MD-2B competitively suppressed NF-kappaB activity induced by LPS. Regardless of the truncation, however, MD-2B still bound to TLR4 as efficiently as MD-2. Flow cytometric analyses revealed that MD-2B inhibited TLR4 from being expressed on the cell surface. Our data indicate that MD-2B may compete with MD-2 for binding to TLR4 and decrease the number of TLR4/MD-2 complexes on the cell surface, resulting in the inhibition of LPS signaling.

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Citations

Jul 28, 2009·The Journal of Biological Chemistry·Pierre TissièresJérôme Pugin
Jan 6, 2007·Hybridoma·Suganya ViriyakosolTheo N Kirkland
May 24, 2014·Nature Reviews. Immunology·Susan CarpenterKatherine A Fitzgerald
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Dec 17, 2010·World Journal of Hepatology·Hui-Lai MiaoFei Zhou
Jul 13, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sergio CandelVictoriano Mulero
Jun 17, 2021·Chinese Medical Journal·Yi-Jing TaoLin Xu

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