Publications by authors named "Beatrice Y C Wan"
Studies of histone deacetylase (HDAC) inhibitors, novel anticancer drugs, in models of autoimmune diseases, asthma, and inflammatory bowel disease suggest that HDAC inhibitors may also have useful anti-inflammatory effects. Accordingly, in vitro studies relevant to asthma and inflammatory bowel disease were conducted using a selection of HDAC inhibitors: suberoylanilide hydroxamic acid (SAHA, Vorinostat), and a related branched hydroxamic acid, diamide (1), MGCD0103 and two short chain fatty acid derivatives: sodium butyrate (of use in inflammatory bowel disease) and sodium valproate. The ability of those HDAC inhibitors to modulate antigen- or agonist-induced contraction of isolated guinea pig tracheal rings and colon, agonist-induced contraction of rat colon, and histamine release from rat peritoneal mast cells was examined.
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- Cyclosporin A (CsA) and tacrolimus (FK506) inhibit T-lymphocytes and mast cells by blocking their activation, though the specific mechanism in mast cells is still unclear.
- Both CsA and FK506 significantly reduce histamine and beta-hexosaminidase release in mast cells, with the drugs affecting membrane repolarization and potassium efflux.
- The drugs also decrease the rise in intracellular calcium levels in response to antigens, indicating they disrupt the secretory process in mast cells through two primary actions: inhibiting the membrane repolarization phase and lowering intracellular calcium concentrations.