title: Lowering of Messenger Ribonucleic Acid Toll-Like Receptors 2-4,9 in Peripheral Blood Mononuclear Cells in Kidney Allograft Recipients, Relationships With Immunosuppressive Treatment, and Delayed Graft Function Occurrence.
abstract: BACKGROUND
  Both tacrolimus (Tac) and cyclosporine (CsA) inhibit control peripheral blood mononuclear cells (PBMC) after stimulation of various Toll-like receptors (TLR) at supra-pharmacological concentrations. Earlier studies demonstrated that 24 hours after kidney transplantation (KT), the expression of the TLR4 messenger RNA (mRNA) in PBMC from patients with subsequent delayed graft function (DGF+) was lower than in patients without DGF (DGF-). An assessment was made of the interaction of immunosuppression with TLR mRNA in PBMC and to verify whether the reduced expression of TLR-2,3,4,9 mRNA in PBMC is permanent in DGF+.
  
  
  METHODS
  We investigated mRNA expression of TLR in non-stimulated PBMC. All patients were transplanted more than 1 month before PBMC acquisition. Patients were divided into groups with respect to positive or negative history of delayed graft function (DGF+/-).
  
  
  RESULTS
  The expression of TLR2, TLR3, and TLR9 in patients was lower than that in the control group. We found an association of Tac C0 with expression of TLR4 only and CsA dose per 1 kg body weight with TLR2 or up to 6 months after KT with TLR9. Mofetil mycophenolate (MMF)contributed to the change of TLR4 expression in the CsA group but not in the Tac group. TLR3 and TLR9 were nearly equally sensitive to both Tac and CsA, with a decrease of expression with respect to control. DGF+ was associated with variable degree of reduction of TLR2, TLR3, TLR4, and TLR 9 expression.
  
  
  CONCLUSIONS
  We showed the importance of immunosuppression and delayed graft function as factors that modify the overall expression of mRNA-TLR PBMC for a period of time after KT. Patients with a history of DGF have chronically decreased expression of mRNA TLR2, TLR3, TLR4, and TLR9. This fact is associated with poorer graft function. Measuring the expression of the TLR in the upper range of therapeutic doses of calcineurin inhibitors and MMF gives the opportunity to assess the strength, effectiveness, and toxicity of immunosuppression.
authors: Department of Nephrology and Transplantation Medicine, Medical University, Wroclaw, Poland. Electronic address: klinef@am.centrum.pl.
authors: S C
authors: SC
authors: Zmonarski
authors: Department of Nephrology and Transplantation Medicine, Medical University, Wroclaw, Poland.
authors: K
authors: K
authors: Kościelska-Kasprzak
authors: Department of Nephrology and Transplantation Medicine, Medical University, Wroclaw, Poland.
authors: M
authors: M
authors: Banasik
authors: Department of Nephrology and Transplantation Medicine, Medical University, Wroclaw, Poland.
authors: M
authors: M
authors: Myszka
authors: Department of Nephrology and Transplantation Medicine, Medical University, Wroclaw, Poland.
authors: M
authors: M
authors: Żabińska
authors: Department of Nephrology and Transplantation Medicine, Medical University, Wroclaw, Poland.
authors: K
authors: K
authors: Madziarska
authors: Department of Nephrology and Transplantation Medicine, Medical University, Wroclaw, Poland.
authors: O
authors: O
authors: Mazanowska
authors: Department of Nephrology and Transplantation Medicine, Medical University, Wroclaw, Poland.
authors: M
authors: M
authors: Krajewska
authors: Department of Nephrology and Transplantation Medicine, Medical University, Wroclaw, Poland.
authors: M
authors: M
authors: Boratyńska
authors: Department of Nephrology and Transplantation Medicine, Medical University, Wroclaw, Poland.
authors: M
authors: M
authors: Klinger
mesh_terms: D000328:Adult; D064591:Allografts; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D051799:Delayed Graft Function / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use; D012333:RNA, Messenger; D016559:Tacrolimus / Q000627:therapeutic use; D051193:Toll-Like Receptors / Q000096:biosynthesis*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus