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2015 ; 12
(2
): 2577-83
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Impact of immunosuppressive agents on the expression of indoleamine
2,3-dioxygenase, heme oxygenase-1 and interleukin-7 in mesangial cells
#MMPMID25936769
Liang GB
; Luo GH
; Bao DS
; Chen AJ
; Zhuang YX
; Guo YN
; Wang X
; Wang YL
; Chen ZP
; Lu YP
; Li YP
Mol Med Rep
2015[Aug]; 12
(2
): 2577-83
PMID25936769
show ga
Chronic allograft nephropathy (CAN) is a major cause of graft loss following
kidney transplantation and may result from the interactions of various immune and
non-immune factors. The aim of the present study was to establish an in vitro
model of glomerular mesangial cell injury in order to examine the gene expression
levels of indoleamine 2,3-dioxygenase (IDO), heme oxygenase-1 (HO-1) and
interleukin-7 (IL-7) in mesangial cells during the healing process as well as to
investigate the effects of various immunosuppressants on the expression of these
genes. The HBZY-1 glomerular mesangial cell line was pre-treated in vitro with
cytochalasin B for 2 h to induce reversible damage. Following the pre-treatment,
the HBZY-1 cells were divided into five groups: Blank control group, cyclosporine
A (CsA) group, tacrolimus (Tac) group, mycophenolate mofetil (MMF) group and
rapamycin (RAPA) group. After treating the mesangial cells with each
immunosuppressive drug for 6, 12 or 24 h, the mRNA and protein expression levels
of IDO, HO-1 and IL-7 were examined using reverse transcription quantitative
polymerase chain reaction (RT-qPCR), western blot and immunohistochemical
analyses. The results showed that expression levels of HO-1 were significantly
upregulated in response to treatment with CsA, FK506, RAPA and MMF, whereas the
expression levels of IL-7 were markedly downregulated by treatment with the above
immunosuppressants. CsA, FK506 and MMF significantly enhanced the expression
levels of IDO, whereas RAPA exhibited no apparent effect on IDO. The present
study may contribute to the understanding of the pathogenesis of CAN and provide
novel strategies for the prevention and treatment of CAN.