Abstract
Purpose:
The cytokines in interleukin (IL)-10 family are known by their anti-infection and anti-inflammatory activities. However, the biology of IL-24, a member of IL-10 family cytokines, is largely unknown, particularly in the ocular tissue. In this study, we investigated the role of IL-24 in a mouse Pseudomonas Aeruginosa (PA) keratitis model.
Methods:
Epithelium-injured B6 mouse corneas were pretreated with or without flagellin for 24h, followed by PA (ATCC 19660) inoculation. Samples were collected at various time points post infection and subjected to PCR and immunofluorescence. Mice were subconjunctivally injected with either IL-24 siRNA to knock down IL-24 expression or mouse IL-24 recombinant protein before the inoculation of PA to explore the biological functions of IL-24.
Results:
PA infection induced IL-24 transcription on corneal epithelial cells; flagellin pretreatment not only alleviated the infection, but also reduced the mRNA expression of IL-24, but not IL-19 and IL-20, the other two members of IL-10 family that share common receptors. STAT3, a signal mediator in IL-24 pathway, was phosphorated in response to PA infection, and p-STAT3 was mainly expressed in the infiltrated cells, indicating that immune cells were recruited and activated by the infection. IL-24 downregulation alleviated the severity of PA keratitis, and the application of IL-24 recombinant protein exacerbated PA infection on mouse cornea.
Conclusions:
These data demonstrate that IL-24 exhibits a detrimental effect on the host defense against PA infection, suggesting that IL-24 pathway may be a new intervention site for treating infectious keratitis.