R Pahwa1,2, S Devaraj3, I Jialal1,2. 1. Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology, Division of Endocrinology, Diabetes and Metabolism, University of California Davis Medical Center, Sacramento, CA, USA. 2. Medical Services, VA Medical Center, Mather, CA, USA. 3. Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
Abstract
BACKGROUND: There is a growinge body of evidence pointing towards an important role for Toll-like receptors (TLR) especially TLR4 in obesity and metabolic syndrome. OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: There is a growinge body of evidence pointing towards an important role for Toll-like receptors (TLR) especially TLR4 in obesity and metabolic syndrome. OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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 humanobesity and metabolic syndrome.
Authors: J M Moreno-Navarrete; F Ortega; M Serino; E Luche; A Waget; G Pardo; J Salvador; W Ricart; G Frühbeck; R Burcelin; J M Fernández-Real Journal: Int J Obes (Lond) Date: 2011-12-20 Impact factor: 5.095
Authors: Philipp M Lepper; Christian Schumann; Kathy Triantafilou; F Maximilian Rasche; Tibor Schuster; Hedwig Frank; E Marion Schneider; Martha Triantafilou; Maximilian von Eynatten Journal: J Am Coll Cardiol Date: 2007-06-18 Impact factor: 24.094
Authors: José María Moreno-Navarrete; Xavier Escoté; Francisco Ortega; Matteo Serino; Mark Campbell; Marie-Caroline Michalski; Martine Laville; Gemma Xifra; Elodie Luche; Pere Domingo; Mónica Sabater; Gerard Pardo; Aurelie Waget; Javier Salvador; Marta Giralt; Jose I Rodriguez-Hermosa; Marta Camps; Catherine I Kolditz; Nathalie Viguerie; Jean Galitzky; Pauline Decaunes; Wifredo Ricart; Gema Frühbeck; Francesc Villarroya; Geltrude Mingrone; Dominique Langin; Antonio Zorzano; Hubert Vidal; Joan Vendrell; Remy Burcelin; Antonio Vidal-Puig; José Manuel Fernández-Real Journal: Diabetologia Date: 2013-08-21 Impact factor: 10.122