title: [Changes in Toll-like receptor 2 and 4 gene expression in vital organs in septic rats and their regulation mechanisms].
abstract: OBJECTIVE
  To investigate the changes in Toll-like receptor (TLR) 2 and 4 gene expression in vital organs in septic rats and their potential regulation mechanism.
  
  
  METHODS
  One hundred Wistar rats were randomly divided into normal controls (n=10), sham-operated group (n=10), septic group (n=60), and recombinant bactericidal/permeability increasing protein (BPI)-treated group (n=20). Severe sepsis was replicated by cecal ligation and puncture (CLP). Animals were sacrificed at different time points after CLP, tissue TLR2/4 mRNA expression in the liver, lungs, kidneys as well as intestine were measured by reverse transcription-polymerase chain reaction (RT-PCR). Plasma levels of tumor necrosis factor-alpha(TNF-alpha) and interleukin-10 (IL-10) were also determined by enzyme linked immunoadsorbent assay (ELISA).
  
  
  RESULTS
  TLR2/4 mRNA could be detected in various tissues with low values both in normal controls and sham-operated group, but they were markedly up-regulated at 2 hours after CLP, peaking at 6-12 hours. Tissue TLR4 mRNA was gradually down-regulated 24 hours later, while TLR2 mRNA levels maintained high values up to 72 hours. In comparison with the CLP group, treatment with BPI significantly decreased TLR2 mRNA in various tissues at 12 and 24 hours (P<0.05 or P<0.01), also tissue TLR4 mRNA at 12 hours (P<0.05 or P<0.01), without marked influence on TLR4 mRNA expression at 24 hours in liver, lungs and small intestine (P>0.05). In addition, treatment with BPI could significantly lower plasma TNF-alpha levels at 12 hours post-CLP, on the other hand markedly elevate plasma IL -10 levels 24 hours later (P<0.01).
  
  
  CONCLUSIONS
  These data suggest that severe peritoneal infection could result in up-regulation of TLR2/4 mRNA expression in vital organs, which might play important roles in mediating proinflammatory cytokine synthesis and release. Endotoxemia appears to be involved in the activation of tissue TLR2/4 expression associated with CLP-induced sepsis.
authors: Burns Institute, 304th Hospital of People's Liberation Army, Beijing 100037, China.
authors: Yong-ming
authors: YM
authors: Yao
authors: Xiao-jian
authors: XJ
authors: Yan
authors: Feng-hua
authors: FH
authors: Yao
authors: Ming-hua
authors: MH
authors: Cheng
authors: Ning
authors: N
authors: Dong
authors: Yan
authors: Y
authors: Yu
authors: Zhi-yong
authors: ZY
authors: Sheng
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000627:therapeutic use; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C021623:bactericidal permeability increasing protein; D016753:Interleukin-10