18β-Glycyrrhetic Acid Inhibits Immune Activation Triggered by HMGB1, a Pro-inflammatory Protein Found in the Tear Fluid during Conjunctivitis and Blepharitis.
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.
Ocul Immunol Inflamm. 2011 Mar 22. [Epub ahead of print]
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.