A new link between steroid resistance, glucocorticoid receptor and nuclear factor kappa B p65 in idiopathic nephrotic syndrome.
OBJECTIVE
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.
Szilagyi
Katarina
K
Department of Pharmacology, Safarik University School of Medicine, Kosice, Slovakia. katarina.szilagyi@gmail.com
Podracka
Ludmila
L
Franke
Niels E
NE
Mojzis
Jan
J
Mirossay
Ladislav
L
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000502:physiology*; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D009404:Nephrotic Syndrome / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D055815:Young Adult
D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D011965:Receptors, Glucocorticoid; D051996:Transcription Factor RelA; C411470:glucocorticoid receptor alpha; D000072000:NF-KappaB Inhibitor alpha