Glucocorticoids exert anti-inflammatory effects partly through non-genomic mechanisms (protein-protein interactions), particularly by inhibiting transcription factors. The key transcription factor that glucocorticoid receptor (GR) directly inhibits through protein-protein interaction (transrepression) in inflammation is:

• A NF-kB (nuclear factor kappa B) ✓
• B STAT3 (signal transducer and activator of transcription 3)
• C CREB (cAMP response element binding protein)
• D Sp1 (specificity protein 1)

Explanation

Ligand-bound GR tethers to and inhibits NF-kB (particularly the p65 subunit), preventing NF-kB from driving transcription of pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha, COX-2, iNOS). This direct protein-protein transrepression is independent of DNA binding by GR and is considered a primary anti-inflammatory mechanism. GR also inhibits AP-1 transcription factor (c-Fos/c-Jun) by similar transrepression. The side effects of glucocorticoids (metabolic, osteoporosis, immunosuppression) are largely attributable to GR transactivation (DNA-binding, inducing genes like PEPCK, TAT, lipocortin); selective glucocorticoid receptor modulators (SEGRMs/SEGRAs) aim to dissociate anti-inflammatory transrepression from metabolic transactivation.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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