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

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-1βwas 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-1βsignaling pathway and reducing the recruitment of neutrophils and macrophages.

The expression of lacrimal androgen-binding proteins in mice Pseudomonas aeruginosa keratitis

AIM: To investigate the expression of lacrimal androgenbinding proteins(ABPs) in mice Pseudomonas aeruginosa(P. aeruginosa) keratitis.METHODS: P. aeruginosa mice model from different gender was developed by intra-stromal injection. The expression of lacrimal ABPs in lacrimal gland specimens from P. aeruginosa keratitis mice was detected by the quantitative polymerase chain reaction(q RT-PCR). Corneal virulence was evaluated based on clinical scores. To study the mechanism of lacrimal ABPs' expression, experimental subjects were pre-treated with 4 E-BP1 inhibitor, and were used to evaluate the expression levels by q RT-PCR.RESULTS: Compared with control groups, the expression of ABPα, ABPη and ABPζ in lacrimal gland from P. aeruginosa keratitis mice had no meaningful changes, while ABPε and ABPδ were significantly higher at 1 d after infection. The expression of ABPδ in lacrimal gland of male mice was higher than female mice, regardless of whether or not P. aeruginosa keratitis occurred. After 4 E-BP1 inhibitor subconjunctival injection or lacrimal injection, the expression of ABPδ and ABPε has no significant change compared with the control group.CONCLUSION: ABPδ and ABPε secreted by mice lacrimal gland may involve in the progress of alleviating the severity of corneal damage in P. aeruginosa keratitis. The expression of ABPδ and ABPε upon P. aeruginosa infection is independent of cap-dependent m RNA translation activated by 4 E-BP1.

CD23 mediated the induction of pro-inflammatory cytokines Interleukin-1 beta and tumor necrosis factors-alpha in Aspergillus fumigatus keratitis

To the Editor:Fungal keratitis is primarily caused by pathogenic fungi species,such as Fusarium solani and Aspergillus fumigatus.The incidence of A.fumigatus has been increased worldwide.[1]Although new therapies have been used for fungal keratitis,the efficacy of antifungal drugs remains unsatisfactory at present.[2]Fungal keratitis is still a challenge for ophthalmologists because of its difficult and delayed diagnosis,as well as the lack of effective drugs and treatment.