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. 2015 Jun 3:15:55.
doi: 10.1186/s12886-015-0041-z.

The role of Syk signaling in antifungal innate immunity of human corneal epithelial cells

Ying Liu  1   2 , Guiqiu Zhao  3 , Jing Lin  4 , Cui Li  5 , Qing Li  6 , Chengye Che  7 , Qian Wang  8 , Liting Hu  9
Affiliations

The role of Syk signaling in antifungal innate immunity of human corneal epithelial cells

Ying Liu et al. BMC Ophthalmol. .

Abstract

Background: Fungal keratitis is a kind of intractable and sight-threatening diseases. Spleen-tyrosine kinase (Syk) is a non-receptor tyrosine kinase, which plays an important role in the signaling pathway of the receptors. In the current study, we investigate the expression and function of Syk in human corneal epithelial cells with Aspergillus fumigatus (A. fumigatus) infection.

Methods: Cultured telomerase-immortalized human corneal epithelial cells (THCEs) were treated with A. fumigatus hyphae with or without treatment of Syk inhibitors. Activation of Syk and the role of Syk in regulating inflammatory cytokines and chemokines expression were evaluated. The mRNA expression was determined by real time PCR, and protein activation was measured by western blotting.

Results: Syk protein was detected in THCEs, and its activation was enhanced after treatment of A. fumigatus hyphae. Expression of inflammatory cytokines (IL-1β and IL-6) and chemokines (IL-8 and CXCL1) mRNA were significantly increased after stimulation of A. fumigatus hyphae in THCEs. Activation of Syk and expression of IL-1β, IL-6, IL-8 and CXCL1 by A. fumigatus hyphae were blocked by Syk inhibitors.

Conclusion: These findings demonstrate that normal human corneal epithelial cells produce Syk, and Syk activation plays an important role in regulating A. fumigatus hyphae-induced inflammatory responses in THCEs.

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Figures

Fig. 1
Fig. 1
A. fumigatus hyphae induced mRNA expression of inflammatory mediators in THCEs. The mRNA expression of inflammatory cytokines (IL-1β and IL-6) and chemokines (IL-8 and CXCL1) in THCEs were evaluated at 4, 8, 16 h. IL-1β (p < 0.01, p < 0.01, p < 0.01), IL-6 (p < 0.05, p < 0.01, p < 0.01), IL-8 (p < 0.01, p < 0.01, p < 0.01) and CXCL1 (p < 0.05, p < 0.01, p < 0.01) mRNA levels were elevated after A. fumigatus hyphae stimulation of 4, 8, 16 h separately compared with untreated normal THCEs. **p < 0.01, *p < 0.05
Fig. 2
Fig. 2
Syk and p-Syk in THCEs before or after A. fumigatus hyphae stimulation. There was no significant difference between infected cells and normal control cells for Syk protein expression. p-Syk was elevated in the infected THCEs compared with the control at 30, 45, and 60 min a. p-Syk levels were upregulated after 30 min incubation with A. fumigatus hyphae and sustained for 45 and 60 min b (p < 0.01, p < 0.01, p < 0.01 separately). **p < 0.01, *p < 0.05 compared with normal control
Fig. 3
Fig. 3
Change of protein and mRNA with or without the pretreatment of Syk inhibitors. After pretreated with PRT062607 and Piceatannol for 30 min before A. fumigatus hyphae stimulation, activation of Syk was inhibited by 1 μM PRT062607 (p < 0.05), 2 μM PRT062607 (p < 0.01), 5 μM Piceatannol (p < 0.05), 10 μM Piceatannol (p < 0.01) a compared with untreated cells. mRNA expression of IL-1β, IL-6, IL-8 and CXCL1 induced by A. fumigatus hyphae were significantly suppressed b. mRNA expression of IL-1β, IL-6, IL-8, CXCL1 downregulated significantly by 1 μM PRT062607, 2 μM PRT062607, 5 μM Piceatannol, 10 μM Piceatannol. **means p < 0.01, *p < 0.05
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