Cyclosporine induces up-regulation of immunoglobulin-like transcripts 3 and 4 expression on and activity of NKL cells.
BACKGROUND
Immunoglobulin-like transcripts (ILTs), which belong to a kind of receptor family discovered recently, are differentially expressed on myeloid and lymphoid cells. Most of them play important roles to regulate human immune responses by interacting with ligands. Cyclosporine (CsA) is frequently used to prevent graft-versus-host disease and treat autoimmune diseases. There are some studies about the effects of CsA on various human immunologic reactions, but its impact on ILT3 and ILT4 expression on natural killer (NK) cells is less well understood.


METHODS
An NKL cell line was exposed to CsA (5, 10, 15, or 20 mg/L) for 12, 24, or 36 hours before real-time quantitative polymerase chain reaction and flow cytometry were used to detect alterations in ILT3 and ILT4 mRNA and protein expressions. NKL cells treated for 36 hours with or without CsA (15 mg/L) and then coincubated with BGC-823 or JEG-3 cells, in cytolytic and proliferative systems measured by Thiazoyl blue tetrazolium bromide assays.


RESULTS
After CsA treatment both RNA and protein levels of ILT3 and ILT4 on NKL cells were increased for 12, 24, or 36 hours. CsA at various concentrations inhibited the proliferation of NKL cells to varying degrees; at 36 hours CsA (15 mg/L) showed greater effects on ILT3 and ILT4 expression and less influence on NKL growth. The ability of NKL cells primed with CsA (15 mg/L) for 36 hours to kill tumor cells was decreased markedly.


CONCLUSIONS
CsA up-regulated the expression of ILT3 and ILT4 on NKL cells, which influenced their cytotoxicity against tumor cells with different expression of HLA-G and proliferation of NKL cells.
Department of Clinical Laboratory Medicine, Qilu Hospital of Shandong University, Jinan, China.
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Si
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Bian
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Jia
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Hou
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Zhang
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D016572:Cyclosporine / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D059951:HLA-G Antigens / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
D059951:HLA-G Antigens; D007166:Immunosuppressive Agents; C491341:LILRB2 protein, human; C107907:LILRB4 protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D016572:Cyclosporine