Thymol Protects against Aspergillus Fumigatus Keratitis by Inhibiting the LOX-1/IL-1β Signaling Pathway

Curr Med Sci. 2022 Jun;42(3):620-628. doi: 10.1007/s11596-022-2512-9. Epub 2022 Mar 15.

Abstract

Objective: To explore the anti-inflammatory effects and mechanisms of action of thymol in Aspergillus fumigatus (A. fumigatus) keratitis.

Methods: The minimum inhibitory concentration of thymol against A. fumigatus was detected. To characterize the anti-inflammatory effects of thymol, mouse corneas and human corneal epithelial cells were pretreated with thymol or dimethyl sulfoxide (DMSO) before infection with A. fumigatus spores. Slit-lamp microscopy, immunohistochemistry, myeloperoxidase detection, quantitative real-time polymerase chain reaction, and Western blotting were used to assess infection. Neutrophil and macrophage recruitment, in addition to the secretion of LOX-1 and IL-1β, were quantified to evaluate the relative contribution of thymol to the inflammatory response.

Results: We confirmed that the growth of A. fumigatus was directly inhibited by thymol. In contrast with the DMSO group, there was a lower degree of inflammation in the mouse corneas of the thymol-pretreated group. This was characterized by significantly lower clinical scores, less inflammatory cell infiltration, and lower expression of LOX-1 and IL-1β. Similarly, in vitro experiments indicated that the production of LOX-1 and IL-1β was significantly inhibited after thymol treatment, in contrast with the DMSO-pretreated group.

Conclusion: Our findings demonstrate that thymol exerted a direct fungistatic activity on A. fumigatus. Furthermore, thymol played a protective role in fungal keratitis by inhibiting LOX-1/IL-1β signaling pathway and reducing the recruitment of neutrophils and macrophages.

Keywords: Aspergillus fumigatus; IL-1β; LOX-1; keratitis; thymol.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Aspergillosis* / drug therapy
  • Aspergillosis* / metabolism
  • Aspergillus fumigatus / metabolism
  • Dimethyl Sulfoxide / therapeutic use
  • Keratitis* / drug therapy
  • Keratitis* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Scavenger Receptors, Class E / metabolism
  • Scavenger Receptors, Class E / therapeutic use
  • Signal Transduction
  • Thymol / pharmacology
  • Thymol / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Scavenger Receptors, Class E
  • Thymol
  • Dimethyl Sulfoxide