Anti-inflammatory effects of hinokitiol on human corneal epithelial cells: an in vitro study

Eye (Lond). 2015 Jul;29(7):964-71. doi: 10.1038/eye.2015.62. Epub 2015 May 8.

Abstract

Purpose: This study assessed the anti-inflammatory effect and mechanism of action of hinokitiol in human corneal epithelial (HCE) cells.

Methods: HCE cells were incubated with different concentrations of hinokitiol or dimethylsulfoxide (DMSO), which served as a vehicle control. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) assay. After polyriboinosinic:polyribocytidylic acid (poly(I:C)) stimulus, cells with or without hinokitiol were evaluated for the mRNA and protein levels of interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-1β (IL-1β) using real-time PCR analysis and an enzyme-linked immunosorbent assay (ELISA), respectively. Nuclear and cytoplasmic levels of nuclear factor kappa B (NF-κB) p65 protein and an inhibitor of NF-κB α (IκBα) were evaluated using western blotting.

Results: There were no significant differences among the treatment concentrations of hinokitiol compared with cells incubated in medium only. Incubating with 100 μM hinokitiol significantly decreased the mRNA levels of IL-8 to 58.77±10.41% (P<0.01), IL-6 to 64.64±12.71% (P<0.01), and IL-1β to 54.19±8.10% (P<0.01) compared with cells stimulated with poly(I:C) alone. The protein levels of IL-8, IL-6, and IL-1β had similar trend. Further analysis revealed that hinokitiol maintained the levels of IκBα and significantly reduced NF-κB p65 subunit translocation to the nucleus which significantly inhibiting the activation of the NF-κB signal pathway.

Conclusion: Hinokitiol showed a significant protective effect against ocular surface inflammation through inhibiting the NF-κB pathway, which may indicate the possibility to relieve the ocular surface inflammation of dry eye syndrome (DES).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blotting, Western
  • Cell Line
  • Cell Survival
  • Dimethyl Sulfoxide / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Epithelium, Corneal / drug effects*
  • Epithelium, Corneal / metabolism
  • Epithelium, Corneal / pathology
  • Gene Expression Profiling
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Monoterpenes / pharmacology*
  • NF-kappa B / antagonists & inhibitors
  • Poly I-C / pharmacology
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Tropolone / analogs & derivatives*
  • Tropolone / pharmacology

Substances

  • Anti-Infective Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • CXCL8 protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Monoterpenes
  • NF-kappa B
  • RNA, Messenger
  • Tropolone
  • Poly I-C
  • beta-thujaplicin
  • Dimethyl Sulfoxide