title: Mycophenolate mofetil affects monocyte Toll-like receptor 4 signaling during mouse renal ischemia/reperfusion injury.
abstract: BACKGROUND
  Mycophenolate mofetil (MMF) has been used to prevent transplant rejection for many years and has been shown to have protective effects against renal failure. The objective was to investigate the effect of MMF on monocyte Toll-like receptor 4 (TLR4) signaling in the early stages of renal ischemia/reperfusion injury (IRI) of mice.
  
  
  METHODS
  Sixty BALB/C mice were randomly divided into two groups: an IRI group, in which renal IRI was induced by clamping the renal pedicles for 45 minutes, and an MMF group, in which MMF was given (40 mg×kg(-1)×d(-1), intraperitoneally) from 2 days before renal IRI. The plasma creatinine level and renal tissue damage of each group mice were observed 6, 12, 24, and 48 hours after reperfusion. The concentration of plasma high-mobility group box 1 (HMGB-1) (TLR4 ligand), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNF-α) and the expression of TLR-4 on monocytes were determined.
  
  
  RESULTS
  The plasma creatinine concentration in the MMF group was lower compared to the IRI group (after reperfusion of 6, 12, 24, or 48 hours, P < 0.05). Pathological analysis showed that the renal damage was slighter, TLR-4 expression was reduced (after reperfusion of 6, 12, 24, or 48 hours, P < 0.05), and the concentration of cytokines in the plasma was lower (P < 0.05) in the MMF group. No differences in the concentrations of HMGB-1 were observed (P > 0.05).
  
  
  CONCLUSIONS
  Monocyte TLR4 signaling is important in the early stage of kidney IRI, but MMF can inhibit it and improve renal function.
authors.affiliation: Department of Nephropathy, Affiliated Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Zhang
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: Zhang
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000097:blood; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011897:Random Allocation; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D024243:HMGB1 Protein; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine; D009173:Mycophenolic Acid