title: MD-2 expression is not required for cell surface targeting of Toll-like receptor 4 (TLR4).
abstract: The cell surface receptor complex formed by TLR4 and myeloid differentiation 2 (MD-2) is engaged when cells are exposed to LPS. Recent studies suggested that surface localization of functional mouse TLR4 (mTLR4) depends on the simultaneous expression of MD-2. As we did not observe a similar requirement, we conducted a comparative study of human TLR4 and mTLR4 surface expression in immune cells derived from the MD-2 knockout mouse and LPS-responsive cell lines and in cells that ectopically express TLR4. Our results indicate that in the human and mouse models, neither TLR4 function nor TLR4 surface targeting requires MD-2 coexpression. Accordingly, we report on one human cell line, which constitutively expresses functional TLR4 on the cell surface in the absence of MD-2 expression.
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, NRB, 370L, 364 Plantation Street, Worcester, MA 01605, USA. alberto.visintin@umassmed.edu
authors.forename: Alberto
authors.initials: A
authors.lastname: Visintin
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Halmen
authors.forename: Naseema
authors.initials: N
authors.lastname: Khan
authors.forename: Brian G
authors.initials: BG
authors.lastname: Monks
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
authors.forename: Egil
authors.initials: E
authors.lastname: Lien
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051218:Lymphocyte Antigen 96 / Q000096:biosynthesis* / Q000172:deficiency / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4