TITLE

Decreased expression of T-cell NF-κB p65 subunit in steroid-resistant nephrotic syndrome

AUTHOR(S)
Aviles, Diego H.; Vehaskari, V. Matti; Manning, Jennifer; Ochoa, Augusto C.; Zea, Arnold H.
PUB. DATE
July 2004
SOURCE
Kidney International;Jul2004, Vol. 66 Issue 1, p60
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Decreased expression of T-cell NF-κB 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-κB (NF-κB) as well as that of lymphokines interleukin (IL)-2, IL-4, and interferon-gamma (IFN-γ) 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-κB 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-γ 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-κB p65 subunit and up-regulation of IL-2 are potential mechanism of glucocorticoid resistance in SRNS.
ACCESSION #
13347253

 

Related Articles

  • Expression of glucocorticoid receptors in mononuclear cells in nephrotic syndrome. Wasilewska, Anna; Zoch-Zwierz, Walentyna; Tomaszewska, Barbara; Wierciński, Ryszard; Stasiak-Barmuta, Anna // Pediatric Nephrology;Aug2003, Vol. 18 Issue 8, p778 

    Coulter flow cytometry was used to determine glucocorticoid receptors (GCR) in the peripheral blood cells of patients with nephrotic syndrome. The expression of GCR in the lymphocytes (CD3/GCR) and monocytes (CD14/GCR) of peripheral blood of 23 (age 4.9±2.7 years) children with...

  • The tumor suppressor effect of the glucocorticoid receptor in skin is mediated via its effect on follicular epithelial stem cells. Chebotaev, D.; Yemelyanov, A.; Zhu, L.; Lavker, R. M.; Budunova, I. // Oncogene;5/10/2007, Vol. 26 Issue 21, p3060 

    Glucocorticoids are potent inhibitors of mouse skin tumorigenesis. The glucocorticoid control of cellular functions is mediated via the glucocorticoid receptor (GR), a well-known transcription factor. Recently, we generated transgenic mice overexpressing GR under control of the keratin5 (K5)...

  • Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis. Budunova, Irina V; Perez, Paloma; Vaden, Valerie R; Spiegelman, Vladimir S; Slaga, Thomas J; Jorcano, Jose L // Oncogene;12/9/99, Vol. 18 Issue 52, p7423 

    To elucidate the possible role of NF-κB in mouse skin carcinogenesis we studied the expression of p50 (NF-κB1), p52 (NF-κB2), p65 (RelA) and IκB-α inhibitor as well as κB-binding activity in adult SENCAR mouse skin, skin papillomas, and squamous cell carcinomas (SCC) generated...

  • Upregulation of Nuclear Factor-Related Kappa B Suggests a Disorder of Transcriptional Regulation in Minimal Change Nephrotic Syndrome. Audard, Vincent; Pawlak, Andr�; Candelier, Marina; Lang, Philippe; Sahali, Djillali // PLoS ONE;Jan2012, Vol. 7 Issue 1, p1 

    Immune mechanisms underlying the pathophysiology of idiopathic nephrotic syndrome, the most frequent glomerular disease in children, are believed to involve a systemic disorder of T cell function and cell mediated immunity. How these perturbations take place remains unclear. We report here that...

  • Upregulation of Nuclear Factor-Related Kappa B Suggests a Disorder of Transcriptional Regulation in Minimal Change Nephrotic Syndrome. Audard, Vincent; Pawlak, André; Candelier, Marina; Lang, Philippe; Sahali, Djillali // PLoS ONE;Jan2012, Vol. 7 Issue 1, p1 

    Immune mechanisms underlying the pathophysiology of idiopathic nephrotic syndrome, the most frequent glomerular disease in children, are believed to involve a systemic disorder of T cell function and cell mediated immunity. How these perturbations take place remains unclear. We report here that...

  • Transcription factors modulating angiotensinogen gene expression in hepatocytes. Brasier, Allan R.; Li, Junyi; Copland, Al // Kidney International;Dec1994, Vol. 46 Issue 6, p1564 

    The gene encoding angiotensinogen is regulated at the transcriptional level in hepatocytes in response to glucocorticoids and inflammatory cytokines (IL-1 and TNF). These hormones activate transcription of the angiotensinogen gene by changing the abundance of DNA binding proteins that interact...

  • Speed, Sensitivity, and Bistability in Auto-activating Signaling Circuits. Hermsen, Rutger; Erickson, David W.; Hwa, Terence // PLoS Computational Biology;Nov2011, Vol. 7 Issue 11, Special section p1 

    Cells employ a myriad of signaling circuits to detect environmental signals and drive specific gene expression responses. A common motif in these circuits is inducible auto-activation: a transcription factor that activates its own transcription upon activation by a ligand or by...

  • Overexpression of p53 protein in human tumors. Inoue, Keiji; Kurabayashi, Atsushi; Shuin, Taro; Ohtsuki, Yuji; Furihata, Mutsuo // Medical Molecular Morphology;Jun2012, Vol. 45 Issue 3, p115 

    According to the current concept of carcinogenesis, neoplastic transformation consists of multistep accumulations of adverse genetic and epigenetic events. p53 is a transcription factor that regulates cellular response to diverse forms of stress through a complex network which monitors genome...

  • Reduced CDX2 Expression Predicts Poor Overall Survival in Patients with Colorectal Cancer. KWANG DAE HONG; DOOSEOK LEE; YOUNGSEOK LEE; SUN IL LEE; HONG YOUNG MOON // American Surgeon;Apr2013, Vol. 79 Issue 4, p353 

    The homeodomain transcription factor CDX2 directs development and maintenance of normal intestinal epithelium. However, the role of CDX2 in colorectal carcinogenesis is poorly understood. Hence, we investigated the CDX2 expression in patients with colorectal cancer and its relationship to tumor...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics