Effect of cyclosporine on expression of MIC in human hepatocytes.
OBJECTIVE
The human major histocompatibility complex class I chain-related antigen A, B (MICA, B) are believed to be "cell stress sensors," which encode stress-inducible surface proteins that bind to NKG2D, an activating receptor of NK, alpha beta and gamma delta T cells. While cyclosporine (CsA) has improved patient and graft survival rates following solid organ transplantation, its clinical use is often limited by acute and chronic toxicity. Besides ischemia-reperfusion injury, which could up-regulate the expression of MIC, the toxicity of CsA may also be another violent stress factor. The purpose of this study was to investigate whether CsA can affect the expression of MIC.


METHODS
Various doses of CsA (5 or 20 microg/mL) was added to cultured human hepatocytes for 1, 3, 5, 8, or 24 hours. The expression of MIC was measured by immunofluorescence using a laser scanning confocal microscope.


RESULTS
CsA (5 or 20 microg/mL) upregulated MIC protein expression in hepatocytes at 1 hour, peaking at 3 hours, and persisting until 5 hours (P < .05), returning to normal levels after 8 to 24 hours (P > .05).


CONCLUSIONS
This study reported that CsA up-regulated MIC expression on human hepatocytes. MIC, as a "cellular stress biomarker," may play a significant role in activating NK, T, and B lymphocyte responses associated with transplantation. This study suggested that immunosuppressants produce deterioration in organ function in transplantation.
He
Y
Y
Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, P.R. China.
Li
S
S
Feng
L
L
Cheng
F
F
Ye
Z
Z
Li
Y
Y
D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007700:Kinetics
D015395:Histocompatibility Antigens Class I; D016572:Cyclosporine