Fouzas Ioannis, Daoudaki M, Sotiropoulos G C, Vrochides D, Papanikolaou V, Imvrios G, Sgourakis G, Molmenti E P, Vavatsi N, Thalhammer T, Takoudas D, Broelsch C E
Organ Transplant Unit, Hippokration Hospital, Aristotle University Medical School, 49, Konstantinoupoleos Ave, Thessaloniki 54642, Greece.
Eur J Med Res. 2008 Apr 30;13(4):154-62.
We have investigated CsA induced liver hyperplasia to explore the potential effects on the immunogenicity of the regenerating liver within the clinical context of rejection after transplantation.
Flow cytometry analysis of hepatocytes, isolated 48 hours after 2/3 partial hepatectomy (PH2/3) or sham operation in rats, was performed to determine the effect of CsA on DNA synthesis and MHC molecule expression. The possible role of PGE2 was evaluated by the administration of SC-19220, an EP1-PGE2 receptor antagonist.
CsA augmented liver regeneration and this was partially attenuated by SC-19220. The moderate expression of class I MHC expression, as well as the very low class II MHC expression detected in normal hepatocytes by flow cytometry was augmented after PH2/3 and reduced by CsA. The CsA-mediated decrease of hepatocyte immunogenicity was not SC-19220 dependent.
It is proposed that the enhancing effect of CsA on hepatocyte proliferation is by means of an indirect mechanism that can be attributed to a) reduced immunogenicity of the regenerating liver as a result of inhibition of class I and II MHC hepatocyte expression and b) increased PGE2 synthesis in the liver mediated by its action on EP1 receptor.
我们研究了环孢素A（CsA）诱导的肝脏增生，以探讨其在移植后排斥反应的临床背景下对再生肝脏免疫原性的潜在影响。
对大鼠进行2/3部分肝切除术（PH2/3）或假手术后48小时分离的肝细胞进行流式细胞术分析，以确定CsA对DNA合成和MHC分子表达的影响。通过给予EP1-PGE2受体拮抗剂SC-19220评估PGE2的可能作用。
CsA增强了肝脏再生，而SC-19220部分减弱了这种作用。通过流式细胞术在正常肝细胞中检测到的I类MHC表达的适度表达以及II类MHC表达的极低水平在PH2/3后增加，并被CsA降低。CsA介导的肝细胞免疫原性降低不依赖于SC-19220。
提出CsA对肝细胞增殖的增强作用是通过一种间接机制，这可归因于：a）由于抑制I类和II类MHC肝细胞表达，再生肝脏的免疫原性降低；b）其对EP1受体的作用介导肝脏中PGE2合成增加。
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