Valproic acid exerts specific cellular and molecular anti-inflammatory effects in post-operative conjunctiva

• DOI: 10.1007/s00109-018-1722-x
• Publication Date: 2018-11-19T12:36:56Z
• Authors: Li-Fong Seet; Li Zhen Toh; Sharon N. Finger; Stephanie W. L. Chu; Tina T. Wong
• Keywords: Valproic Acid; Human genetics

Valproic acid (VPA) is a histone deacetylase inhibitor used clinically for neurological disorders. It also potentially useful as anti-fibrotic therapy it reduced collagen deposition in the post-operative conjunctiva. In this study, we further evaluated effects of VPA on inflammation using mouse model conjunctival scarring. VPA, injected into subconjunctiva immediately after surgery, did not cause any adverse tissue response when examined by live microscopy and produced an apparent reduction proinflammatory proangiogenic markers immunohistological examinations. In-depth analyses treated operated tissues revealed that selectively inhibited CD45highF4/80low macrophage subset well production specific cytokines/ chemokines, including CXCL1, IL-5, IL-6, IL-10 which were ≥ 2.0-fold. specifically NF-кB2 p100 protein mean 3.87-fold. On fibroblasts, treatment resulted decreased secretion cytokines, CCL2, VEGF-A, IL-15. presence TNF-α, induction cytokines/chemokines, notably CCL5 p100. corroboration, suppressed TNF-α stimulation NF-кB reporter transcription 1.51-fold. These data indicate can modulate both cellular molecular targets selective manner may therefore attenuate surgery-induced inflammation. previous findings suggest that, suppressing key mediators fibrosis, therapeutic improving surgical outcome involving