Decreased expression of T-cell NF-kappaB p65 subunit in steroid-resistant nephrotic syndrome
BACKGROUND: Although the etiology of childhood nephrotic syndrome is unclear, there is evidence to suggest an important role for T cells in the pathogenesis. Steroid resistance is considered a poor prognostic sign but the mechanism of the resistance is unknown. The study examined the potential role of T-cell nuclear transcription factors in the steroid resistance.
METHODS: The expression of the nuclear transcription factors activating protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) as well as that of lymphokines interleukin (IL)-2, IL-4, and interferon-gamma (IFN-gamma) were compared in T cells obtained from normal subjects, children with steroid-sensitive nephrotic syndrome (SSNS) and children with steroid-resistant nephrotic syndrome (SRNS) before any treatment was given. Changes in expression and binding of the nuclear transcription factors were studied with electrophoretic mobility shift assay (EMSA) and Western blot, whereas mRNA cytokine expression were evaluated by enzyme-linked immunosorbent assay (ELISA)-linked reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS: A significant decrease of the p65 subunit protein of NF-kappaB but not in p50 was documented by both EMSA (N= 7) and Western blotting (N= 5) in five of five SRNS patients but not in control subjects or SSNS patients; there was a decrease in mRNA expression as shown by ELISA-linked RT-PCR. In contrast, there were no significant differences in AP-1 expression by EMSA. IL-2 mRNA level was higher in T cells from SRNS patients than in T cells from either SSNS or control subjects. IL-4 and IFN-gamma were equally decreased in both groups of patients.
CONCLUSION: The results show differences in T cells between untreated SSNS and SRNS patients. The decrease of NF-kappaB p65 subunit and up-regulation of IL-2 are potential mechanism of glucocorticoid resistance in SRNS.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2004 |
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| Erschienen: |
2004 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:66 |
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| Enthalten in: |
Kidney international - 66(2004), 1 vom: 01. Juli, Seite 60-7 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Aviles, Diego H [VerfasserIn] |
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| Anmerkungen: |
Date Completed 03.01.2005 Date Revised 21.11.2008 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM148876072 |
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| 041 | |a eng | ||
| 100 | 1 | |a Aviles, Diego H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Decreased expression of T-cell NF-kappaB p65 subunit in steroid-resistant nephrotic syndrome |
| 264 | 1 | |c 2004 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Completed 03.01.2005 | ||
| 500 | |a Date Revised 21.11.2008 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Although the etiology of childhood nephrotic syndrome is unclear, there is evidence to suggest an important role for T cells in the pathogenesis. Steroid resistance is considered a poor prognostic sign but the mechanism of the resistance is unknown. The study examined the potential role of T-cell nuclear transcription factors in the steroid resistance | ||
| 520 | |a METHODS: The expression of the nuclear transcription factors activating protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) as well as that of lymphokines interleukin (IL)-2, IL-4, and interferon-gamma (IFN-gamma) were compared in T cells obtained from normal subjects, children with steroid-sensitive nephrotic syndrome (SSNS) and children with steroid-resistant nephrotic syndrome (SRNS) before any treatment was given. Changes in expression and binding of the nuclear transcription factors were studied with electrophoretic mobility shift assay (EMSA) and Western blot, whereas mRNA cytokine expression were evaluated by enzyme-linked immunosorbent assay (ELISA)-linked reverse transcription-polymerase chain reaction (RT-PCR) | ||
| 520 | |a RESULTS: A significant decrease of the p65 subunit protein of NF-kappaB but not in p50 was documented by both EMSA (N= 7) and Western blotting (N= 5) in five of five SRNS patients but not in control subjects or SSNS patients; there was a decrease in mRNA expression as shown by ELISA-linked RT-PCR. In contrast, there were no significant differences in AP-1 expression by EMSA. IL-2 mRNA level was higher in T cells from SRNS patients than in T cells from either SSNS or control subjects. IL-4 and IFN-gamma were equally decreased in both groups of patients | ||
| 520 | |a CONCLUSION: The results show differences in T cells between untreated SSNS and SRNS patients. The decrease of NF-kappaB p65 subunit and up-regulation of IL-2 are potential mechanism of glucocorticoid resistance in SRNS | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Interleukin-2 |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a NF-kappa B p50 Subunit |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Steroids |2 NLM | |
| 650 | 7 | |a Transcription Factor AP-1 |2 NLM | |
| 650 | 7 | |a Transcription Factor RelA |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
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| 700 | 1 | |a Matti Vehaskari, V |e verfasserin |4 aut | |
| 700 | 1 | |a Manning, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Ochoa, Augusto C |e verfasserin |4 aut | |
| 700 | 1 | |a Zea, Arnold H |e verfasserin |4 aut | |
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