title: Differential pro-inflammatory responses of TNF-α receptors (TNFR1 and TNFR2) on LOX-1 signalling.
abstract: TNF-α potently induces LOX-1 expression in THP-1 macrophages at concentrations between 1.25-50 ng/mL. The interplay between the two TNF receptors (TNFR1 and TNFR2) was apparent in the expression pattern of LOX-1 in response to TNF-α. Interestingly, R1 signal abrogation depleted both TNFR2 as well as LOX-1 transcript expression, suggesting that TNFR1 holds priority in the relative signaling mechanism between TNFR1 and TNFR2. TNF-α was also found to abrogate the oxidized-LDL (ox-LDL) mediated increase in intracellular pool of NO, a known downstream intermediate of LOX-1 pro-inflammatory signaling cascade. At the level of ox-LDL clearance, TNF-α inhibited the uptake (scavenging) of ox-LDL via LOX-1. Our study demonstrates the ability of TNF-α to enhance the signaling propensity of LOX-1 by increasing its expression and inhibiting its scavenging property.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, 110029, India, albinaarjuman@hotmail.com.
authors.forename: Albina
authors.initials: A
authors.lastname: Arjuman
authors.forename: Nimai C
authors.initials: NC
authors.lastname: Chandra
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000493:pharmacokinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009636:Norbornanes; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D001952:Bridged-Ring Compounds; D008077:Lipoproteins, LDL; D009636:Norbornanes; C495137:OLR1 protein, human; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D051127:Scavenger Receptors, Class E; D013859:Thiocarbamates; D013871:Thiones; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide; C046498:tricyclodecane-9-yl-xanthogenate