title: Lipopolysaccharide Induced Activation of Toll Like Receptor 4 in Isolated Rat Heart Suggests a Local Immune Response in Myocardium.
abstract: BACKGROUND
  Myocardial dysfunction is one of the major complications in patients with sepsis where there is a relationship between the blood level of cytokines and the onset of myocardial depression. In many cases of sepsis, the presence of Lipopolysaccharide (LPS) has been established. LPS Binding Protein (LBP) bound endotoxin is recognized by CD14/toll-like receptor-4 (TLR4) complexes in innate immune cells which stimulates TNF-α release.
  
  
  OBJECTIVE
  To investigate whether isolated rat heart is capable of producing TNF-α locally through TLR4 activation by LPS.
  
  
  METHODS
  Using langendorff method, LPS in 120 mL of the modified Krebs-Henseleit buffer solution (KHBS) at final concentration of 1 µg/mL was perfused at recycling mode. The effect of LPS on cardiac function was evaluated. To assess the TLR4 activity and TNF-α release, western blotting, real time-PCR, and ELISA were used.
  
  
  RESULTS
  Compared with control, coronary perfusion pressure (CPP) as well as left ventricular developed pressure (LVDP), maximum and minimum rates of the left ventricular developed pressure (dP/dtmax; dP/dtmin; p<0.001) were depressed to a maximum level after 180 minutes recycling with LPS. This myocardial depression was associated with a significant increase in TLR4 expression (p<0.01), MyD88 activity (p<0.01) and TNF-α (p<0.05) concentration in the heart tissue.
  
  
  CONCLUSIONS
  The results of this study show that heart is capable of producing TNF-α through TLR4 and MyD88 activation independent of classic immune system and suggest a local immune response.
authors.affiliation: Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rameshrad
authors.forename: Nasrin
authors.initials: N
authors.lastname: Maleki-Dizaji
authors.forename: Haleh
authors.initials: H
authors.lastname: Vaez
authors.forename: Hamid
authors.initials: H
authors.lastname: Soraya
authors.forename: Ailar
authors.initials: A
authors.lastname: Nakhlband
authors.forename: Alireza
authors.initials: A
authors.lastname: Garjani
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004789:Enzyme Activation; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D009206:Myocardium / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C507781:Myd88 protein, rat; C495347:Tlr4 protein, rat