Molecular mechanism of glucocorticoid resistance in inflammatory bowel disease

Table 1 Factors involved in glucocorticoid resistance

GR	Reduced GR mRNA expression[42]
	Reduced GC binding affinity[43]
	Polymorphisms in the NR3C1 gene[45]
GR heterocomplex	Altered expression of the chaperones and co-chaperones that make up the heterocomplex[74-78]
	Polymorphisms in the Hsp90 gene[79]
	Genetic variations in the STIP1 gene coding for Hop[79]
Nuclear transport factors	Polymorphisms in the Importin 13 gene[86]
Transcription machinery	Lower expression of SMARCB1 in resistant leukaemia cells[97]
Pro-inflammatory mediators	Polymorphisms in the NALP1 gene[72]
	TNF-α promoter SNP correlated with steroid response in several disease[149-154]
	IL-10 polymorphisms related with a positive prednisone response in children with ALL[159]
P-gp	Hyperexpression of P-gp in lymphocytes and epithelial cells from GC-resistant IBD patients[167]

GR: Glucocorticoid receptor; GC: Glucocorticoid; Hsp: Heat-shock protein; Hop: Hsp70/Hsp90 organization protein; P-gp: P-glycoprotein; NR3C1: Nuclear receptor subfamily 3, group C, member 1; NALP1: NACHT leucine-rich-repeat protein 1; SNP: Single nucleotide polymorphism; TNF-α: Tumor necrosis factor α; IL: Interleukin; ALL: Acute lymphoblastic leukemia; IBD: Inflammatory bowel disease.