A new link between steroid resistance, glucocorticoid receptor and nuclear factor kappa B p65 in idiopathic nephrotic syndrome.

Szilagyi K, Podracka L, Franke N, Mojzis J, Mirossay L.
  Vol. 30 (5) 2009 Neuro endocrinology letters Journal Article   2009; 30(5): 629-636 PubMed PMID:  20035271    Citation  Keywords:  Adolescent, Child, Child, Preschool, Drug Resistance:physiology, Female, Humans, I-kappa B Proteins:metabolism, Male, NF-KappaB Inhibitor alpha, Nephrotic Syndrome:metabolism, Receptors, Glucocorticoid:metabolism, Transcription Factor RelA:metabolism, You.   

OBJECTIVES: The aim of our study was to investigate levels of glucocorticoid receptor (GRalpha), nuclear factor kappa B (NFkappaB) p65/p50 and inhibitor of NFkappaB alpha (IkappaBalpha) in the peripheral mononuclear blood cells (PMBC) of children with idiopathic nephrotic syndrome (INS).

METHODS: The expression of GRalpha, NFkappaBp65/p50 and IkappaBalpha was determined in 59 patients (age 10.2+/-5.1) and 25 healthy controls (CO) (age 13.1+/-3.4) using Western blot analysis. Patients were labeled according to their clinical sensitivity to glucocorticoids (GCs) as responders (RE), partial responders (PR), and non-responders (NR).

RESULTS: Significantly higher expressions of GRalpha were observed in RE than in PR, NR (p<0.01) and even CO (p<0.05). Similarly, expression of NFkappaBp65 was higher in RE in comparison to PR, NR and CO (p<0.05). These differences were more emphasized in the relapse: levels of GRalpha were significantly lower in PR than in RE and CO (p<0.01). Significant differences were also observed in expression of NFkappaB: RE showed significantly higher expression of NFkappaBp65 in comparison to PR, NR and even CO (p<0.01).

CONCLUSIONS: Lower levels of both GRalpha and NFkappaBp65 are associated with poor or no response to GCs and the difference is more pronounced in patients experiencing relapse of INS.

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