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Increase of Th17 Cell Phenotype in Kidney Transplant Recipients with Chronic Allograft Dysfunction.

Chung BH, Kim KW, Kim BM, Doh KC, Cho ML, Yang CW - PLoS ONE (2015)

Bottom Line: We also performed in vitro study using human proximal renal tubular epithelial cell line (HPRTEpiC) to evaluate the effect of IL-17 on human renal tubular epithelial cells.The CAD group showed increased percentage of Th17 cells out of CD4+ T cells and also increased proportion of IL-17 producing cells out of effector memory T cells or out of CCR4+CCR6+/CD4+ T cells compared to the LTS group and other control groups.Also, the serum level of IL-17, IL-33, and RAGE, and the expression of IL-1beta, RAGE, and HMGB1 mRNA showed an increase in the CAD group compared to the LTS group.

View Article: PubMed Central - PubMed

Affiliation: Convergent Research Consortium for Immunologic disease, St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul, Seoul, Korea.

ABSTRACT
This study was performed to determine the association of Th17 cell phenotype with chronic allograft dysfunction in kidney transplant recipients (KTRs). We compared the expression of Th17 cell phenotype in KTRs with chronic allograft dysfunction group (CAD, n = 52) with four control groups (long-term stable KTRs (LTS, n = 67), early stable KTRs (ES, n = 28), end stage renal disease (ESRD, n = 45), and healthy control (HC, n = 26). We also performed in vitro study using human proximal renal tubular epithelial cell line (HPRTEpiC) to evaluate the effect of IL-17 on human renal tubular epithelial cells. The CAD group showed increased percentage of Th17 cells out of CD4+ T cells and also increased proportion of IL-17 producing cells out of effector memory T cells or out of CCR4+CCR6+/CD4+ T cells compared to the LTS group and other control groups. Also, the serum level of IL-17, IL-33, and RAGE, and the expression of IL-1beta, RAGE, and HMGB1 mRNA showed an increase in the CAD group compared to the LTS group. In vitro study revealed that IL-17 increased production of IL-6 and IL-8 and up-regulated profibrotic gene expression such as ACTA-2 and CTGF in HPRTEpiC in a dose-dependent manner, which suggests that IL-17 has a role in the development of renal tubular cell injury. The results of our study may suggest that increase of Th17 cell phenotype could be a marker for the chronic allograft injury; hence there is a need to develop diagnostic and therapeutic tools targeting the Th17 cells pathway.

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Expression of acute and chronic injury markers in renal tubular cells treated with recombinant human IL-17.Renal tubular epithelial cell were cultured with rhIL-17 (0, 10, 50, or 100 ng/ml) for 72 hours, and the production of (A) IL-6 and (B) IL-8 was measured using ELISA. Renal tubular epithelial cell were cultured with rhIL-17 (0, 10, 50, or 100 ng/ml) for 72 hours, and the expression of (C)ACTA-2 and (D)CTGF mRNA, relative to β-actin, was measured using real-time polymerase chain reaction. Bars show the means. *P<0.05 vs. Nil, †P<0.05 vs. IL-17 10.
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pone.0145258.g007: Expression of acute and chronic injury markers in renal tubular cells treated with recombinant human IL-17.Renal tubular epithelial cell were cultured with rhIL-17 (0, 10, 50, or 100 ng/ml) for 72 hours, and the production of (A) IL-6 and (B) IL-8 was measured using ELISA. Renal tubular epithelial cell were cultured with rhIL-17 (0, 10, 50, or 100 ng/ml) for 72 hours, and the expression of (C)ACTA-2 and (D)CTGF mRNA, relative to β-actin, was measured using real-time polymerase chain reaction. Bars show the means. *P<0.05 vs. Nil, †P<0.05 vs. IL-17 10.

Mentions: HRPTEpiCs were cultured with three different doses of rhIL-17 (10, 50, 100 ng/ml) and we measured the IL-6 or IL-8 level after 72-hour incubation. Fig 7A and 7B showed that all three doses of rhIL-17 treatment induced significantly increased production of IL-6 or IL-8 in a dose-dependent manner (P<0.05 vs. Nil for each comparison). The effect of IL-17 on pro-fibrotic gene expression in HRPTEpiCs was examined as well. As shown in Fig 7C and 7D, all three doses of rhIL-17 significantly increased the expression of ACTA-2 (α-SMA) and CTGF (connective tissue growth factor) genes in a dose-dependent manner as well (P<0.05 vs. Nil for each comparison).


Increase of Th17 Cell Phenotype in Kidney Transplant Recipients with Chronic Allograft Dysfunction.

Chung BH, Kim KW, Kim BM, Doh KC, Cho ML, Yang CW - PLoS ONE (2015)

Expression of acute and chronic injury markers in renal tubular cells treated with recombinant human IL-17.Renal tubular epithelial cell were cultured with rhIL-17 (0, 10, 50, or 100 ng/ml) for 72 hours, and the production of (A) IL-6 and (B) IL-8 was measured using ELISA. Renal tubular epithelial cell were cultured with rhIL-17 (0, 10, 50, or 100 ng/ml) for 72 hours, and the expression of (C)ACTA-2 and (D)CTGF mRNA, relative to β-actin, was measured using real-time polymerase chain reaction. Bars show the means. *P<0.05 vs. Nil, †P<0.05 vs. IL-17 10.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696852&req=5

pone.0145258.g007: Expression of acute and chronic injury markers in renal tubular cells treated with recombinant human IL-17.Renal tubular epithelial cell were cultured with rhIL-17 (0, 10, 50, or 100 ng/ml) for 72 hours, and the production of (A) IL-6 and (B) IL-8 was measured using ELISA. Renal tubular epithelial cell were cultured with rhIL-17 (0, 10, 50, or 100 ng/ml) for 72 hours, and the expression of (C)ACTA-2 and (D)CTGF mRNA, relative to β-actin, was measured using real-time polymerase chain reaction. Bars show the means. *P<0.05 vs. Nil, †P<0.05 vs. IL-17 10.
Mentions: HRPTEpiCs were cultured with three different doses of rhIL-17 (10, 50, 100 ng/ml) and we measured the IL-6 or IL-8 level after 72-hour incubation. Fig 7A and 7B showed that all three doses of rhIL-17 treatment induced significantly increased production of IL-6 or IL-8 in a dose-dependent manner (P<0.05 vs. Nil for each comparison). The effect of IL-17 on pro-fibrotic gene expression in HRPTEpiCs was examined as well. As shown in Fig 7C and 7D, all three doses of rhIL-17 significantly increased the expression of ACTA-2 (α-SMA) and CTGF (connective tissue growth factor) genes in a dose-dependent manner as well (P<0.05 vs. Nil for each comparison).

Bottom Line: We also performed in vitro study using human proximal renal tubular epithelial cell line (HPRTEpiC) to evaluate the effect of IL-17 on human renal tubular epithelial cells.The CAD group showed increased percentage of Th17 cells out of CD4+ T cells and also increased proportion of IL-17 producing cells out of effector memory T cells or out of CCR4+CCR6+/CD4+ T cells compared to the LTS group and other control groups.Also, the serum level of IL-17, IL-33, and RAGE, and the expression of IL-1beta, RAGE, and HMGB1 mRNA showed an increase in the CAD group compared to the LTS group.

View Article: PubMed Central - PubMed

Affiliation: Convergent Research Consortium for Immunologic disease, St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul, Seoul, Korea.

ABSTRACT
This study was performed to determine the association of Th17 cell phenotype with chronic allograft dysfunction in kidney transplant recipients (KTRs). We compared the expression of Th17 cell phenotype in KTRs with chronic allograft dysfunction group (CAD, n = 52) with four control groups (long-term stable KTRs (LTS, n = 67), early stable KTRs (ES, n = 28), end stage renal disease (ESRD, n = 45), and healthy control (HC, n = 26). We also performed in vitro study using human proximal renal tubular epithelial cell line (HPRTEpiC) to evaluate the effect of IL-17 on human renal tubular epithelial cells. The CAD group showed increased percentage of Th17 cells out of CD4+ T cells and also increased proportion of IL-17 producing cells out of effector memory T cells or out of CCR4+CCR6+/CD4+ T cells compared to the LTS group and other control groups. Also, the serum level of IL-17, IL-33, and RAGE, and the expression of IL-1beta, RAGE, and HMGB1 mRNA showed an increase in the CAD group compared to the LTS group. In vitro study revealed that IL-17 increased production of IL-6 and IL-8 and up-regulated profibrotic gene expression such as ACTA-2 and CTGF in HPRTEpiC in a dose-dependent manner, which suggests that IL-17 has a role in the development of renal tubular cell injury. The results of our study may suggest that increase of Th17 cell phenotype could be a marker for the chronic allograft injury; hence there is a need to develop diagnostic and therapeutic tools targeting the Th17 cells pathway.

Show MeSH
Related in: MedlinePlus