18β-Glycyrrhetic Acid Inhibits Immune Activation Triggered by HMGB1, a Pro-inflammatory Protein Found in the Tear Fluid during Conjunctivitis and Blepharitis.
Purpose: High-mobility group proteins are chromatin-binding factors with key roles in nuclear homeostasis. Evidence indicates that extracellularly released high-mobility group box 1 protein (HMGB1) behaves as a cytokine, promoting inflammation and disease pathogenesis. HMGB1 release occurs during endophtalmitis or uveoretinitis.
Methods: The authors investigated the presence of HMGB1 in tear fluid of patients with different inflammatory disorders of the external eye.
Results: Data demonstrate that HMGB1 content is close to detection limit in tears of control subjects but highly increased (about 15-fold) in patients with conjunctivitis or blepharitis. The authors also report that 18β-glycyrrhetic acid impairs antibody recognition of HMGB1, suggesting direct binding to the protein. Accordingly, 18β-glycyrrhetic acid prevented HMGB1-dependent COX2 expression and cluster formation in primary cultures of human macrophages.
Conclusion: Together, these findings suggest that HMGB1 contributes to inflammatory disorders of the external eye, and 18β-glycyrrhetic acid may scavenge the protein and inhibit its detrimental effects.
Methods: The authors investigated the presence of HMGB1 in tear fluid of patients with different inflammatory disorders of the external eye.
Results: Data demonstrate that HMGB1 content is close to detection limit in tears of control subjects but highly increased (about 15-fold) in patients with conjunctivitis or blepharitis. The authors also report that 18β-glycyrrhetic acid impairs antibody recognition of HMGB1, suggesting direct binding to the protein. Accordingly, 18β-glycyrrhetic acid prevented HMGB1-dependent COX2 expression and cluster formation in primary cultures of human macrophages.
Conclusion: Together, these findings suggest that HMGB1 contributes to inflammatory disorders of the external eye, and 18β-glycyrrhetic acid may scavenge the protein and inhibit its detrimental effects.
Cavone L, Muzzi M, Mencucci R, Sparatore B, Pedrazzi M, Moroni F, Chiarugi A.
Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy.