title: Ischaemia-induced up-regulation of Toll-like receptor 2 in circulating monocytes in cardiogenic shock.
abstract: OBJECTIVE
  To investigate the role of Toll-like receptor 2 (TLR2) in uncomplicated acute myocardial infarction (AMI) and in cardiogenic shock (CS).
  
  
  RESULTS
  In patients with uncomplicated AMI (n = 20), CS (n = 30) and in age-matched healthy controls (HC; n = 20), TLR2 expression on monocytes was assessed by flow cytometry. Tumour necrosis factor alpha (TNFα) and interleukin-6 (IL6) expression in monocytes was analysed by intracellular cytokine staining. TLR2 expression was increased in patients with AMI compared with HC [mean fluorescence intensity (MFI) 111.1 ± 8.2 vs. 66.9 ± 1.5, P < 0.001]. In patients with CS, TLR2 expression was further increased (132.8 ± 5.6 MFI, P = 0.009 vs. AMI). This was accompanied by an increased expression of the proinflammatory cytokines TNFα (4.3 ± 1.6% in AMI vs. 20.5 ± 5.9% in CS, P = 0.004) and IL6 (6.3 ± 1.6% in AMI vs. 20.6 ± 6.2% in CS, P = 0.032). Furthermore, in all patients with myocardial infarction (AMI + CS; n = 50), a strong correlation between the monocytic TLR2 expression and the symptom to reperfusion time (r(2)= 0.706, P < 0.001) was found, implying tissue hypoxia dependency. Symptom to reperfusion time is a main factor to influence TLR2 expression but not the presence of CS. TLR2 expression of mononuclear cells exposed in vitro to hypoxia was assessed by flow cytometry and western blot. In vitro measurements showed a hypoxia-mediated monocytic TLR2 expression up-regulation.
  
  
  CONCLUSIONS
  We demonstrate TLR2 up-regulation and increased proinflammatory cytokine expression in circulating monocytes in AMI/CS depending on disease severity, implying an important role of TLR2 expression in ischaemic injury.
authors: Klinik für Innere Medizin III,  Universitätsklinikum des Saarlandes, D-66421 Homburg/Saar,  Germany.
authors: Simina
authors: S
authors: Selejan
authors: Janine
authors: J
authors: Pöss
authors: Felix
authors: F
authors: Walter
authors: Matthias
authors: M
authors: Hohl
authors: Ralf
authors: R
authors: Kaiser
authors: Andrey
authors: A
authors: Kazakov
authors: Michael
authors: M
authors: Böhm
authors: Andreas
authors: A
authors: Link
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002116:Calcitonin / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism*; D011498:Protein Precursors / Q000494:pharmacology; D012770:Shock, Cardiogenic / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D011498:Protein Precursors; D051195:Toll-Like Receptor 2; D002116:Calcitonin