title: The effect of the accessory proteins, soluble CD14 and lipopolysaccharide-binding protein on Toll-like receptor 4 activity in human monocytes and adipocytes.
abstract: There is a growinge body of evidence pointing towards an important role for Toll-like receptors (TLR) especially TLR4 in obesity and metabolic syndrome.
  
  
  
  Owing to the paucity of data on the effect of the accessory proteins, lipopolysaccharide (LPS)-binding protein (LBP) and soluble CD14 (sCD14) on TLR4 activation, the present study was undertaken to examine the effect of sCD14 and LBP on TLR4 activation in pivotal cells of meta-inflammation, monocytes and adipocytes.
  
  
  
  The dose-response effects of sCD14 and LBP on TLR4 protein abundance in monocytes obtained from normal human volunteers was determined by flow cytometry and in human-differentiated adipocytes by western blotting. Additionally, the nuclear factor-kappaB (NF-κB) p65 and downstream biomediators interleukin (IL)-1β, IL-8, IL-6 and tumor necrosis factor (TNF)-α were measured in the cell culture supernatants by ELISA (enzyme-linked immunosorbent assay).
  
  
  
  In LPS-primed monocytes, sCD14 but not LBP, augments both TLR4 abundance and inflammatory biomediators (IL-1β, IL-8, IL-6 and TNF-α).sCD14 also showed a similar effect in LPS-primed human adipocytes by augmenting TLR4 protein expression and activity in terms of NF-κB p65 and downstream biomediators (IL-1β, IL-8, IL-6 and TNF-α). LBP at the highest concentration only promoted secretion of IL-8 and TNF-α. However in both monocytes and adipocytes, the effect of sCD14 was superior to LBP.
  
  
  
  In the present report, we make the novel observation that sCD14 compared with LBP, offers a preferred target to ameliorate TLR especially TLR4-induced inflammation and insulin resistance in human obesity and metabolic syndrome.
authors.affiliation: Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology, Division of Endocrinology, Diabetes and Metabolism, University of California Davis Medical Center, Sacramento, CA, USA.|Medical Services, VA Medical Center, Mather, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pahwa
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Devaraj
authors.affiliation: Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology, Division of Endocrinology, Diabetes and Metabolism, University of California Davis Medical Center, Sacramento, CA, USA.|Medical Services, VA Medical Center, Mather, CA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Jialal
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C495345:TLR4 protein, human