LAUSR

Recent studies show that Interleukin-17 (IL-17) family cytokines are directly involved in host immune responses against respiratory bacterial infection and in particular, IL-17C is highly induced in bacterial infected respiratory epithelium. Our study is focused on the therapeutic control of Pseudomonas aeruginosa in upper airway and was designed to demonstrate IL-17C-induced immune response against Pseudomonas aeruginosa (PAO1) infection in nasal epithelium. Passage-2 normal human nasal epithelial (NHNE) cells were infected with PAO1 and IL-17C-related immune responses and therapeutic mechanism of recombinant IL-17C (rhIL-17C) against PAO1 infection were assessed depending on method of inoculation. Microarray data showed that IL-17C expression increased 34.7 times at 8 hr post-infection (hpi) and IL-17C mRNA levels were induced until 48 hpi in PAO1-infected NHNE cells. The PAO1 colonies significantly increased from 8 hpi in NHNE cells and siderophore activity which means iron absorption capacity of PAO1 was enhanced in the supernatants of PAO1-infected NHNE cells. Interestingly, PAO1 mRNA level was reduced in PAO1-infected NHNE cells inoculated with rhIL-17C and supernatants from NHNE cells treated with rhIL-17C also exhibited decreased PAO1 colonies. We found that the siderophore activity of PAO1 was significantly reduced in the supernatants of NHNE cells treated with rhIL-17C where LCN2 expression was highly elevated. These data indicate that IL-17C mediates an antibacterial effect in PAO1-infected NHNE cells by inhibiting reducing siderophore activity of PAO1. Thus, we propose that IL-17C might be an efficient mediator to suppress Pseudomonas aeruginosa infection through disturbing iron absorption of Pseudomonas in nasal epithelium.