title: 18β-glycyrrhetic acid inhibits immune activation triggered by HMGB1, a pro-inflammatory protein found in the tear fluid during conjunctivitis and blepharitis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Cavone
authors.forename: Mirko
authors.initials: M
authors.lastname: Muzzi
authors.forename: Rita
authors.initials: R
authors.lastname: Mencucci
authors.forename: Bianca
authors.initials: B
authors.lastname: Sparatore
authors.forename: Marco
authors.initials: M
authors.lastname: Pedrazzi
authors.forename: Flavio
authors.initials: F
authors.lastname: Moroni
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiarugi
mesh_terms: D000328:Adult; D000906:Antibodies / Q000187:drug effects / Q000276:immunology; D001762:Blepharitis / Q000276:immunology*; D002478:Cells, Cultured; D003231:Conjunctivitis / Q000276:immunology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D013666:Tears / Q000378:metabolism*
chemical_list: D000906:Antibodies; D024243:HMGB1 Protein; C119129:18alpha-glycyrrhetinic acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D006034:Glycyrrhetinic Acid