|-Corticosteroid receptor isoforms:
- Decreased corticosteroid receptor α isoform.
- Increased corticosteroid receptor β isoform.
- Imbalance of the ratio between these two corticosteroid receptor isoforms.
|-Increased expression of pro
- inflammatory transcription factors, such as:
- Nuclear factor kappa beta (NF-kβ)
- Activator protein-1 (AP-1)
|-Corticosteroid receptor modifications: Increased phosphorylation of residues decreases nuclear translocation capacity.
GRα phosphorylation at Ser226 contributes to steroid resistance by preventing nuclear traslocation. This residue has been described to be phosphorylated by:
- Activation of p38 mitogen activated map kinase (p38MAPK).
- Increase in extracellular signal- regulated kinase (ERK).
- Increase in c-Jun N-terminal kinase (JNK)
- Decrease in MKP1.
|-Defect in histone acetylation.