Abstract
Purpose/Aim: Viral infection of the cornea can result in inflammation and scarring and eventually lead to blindness. Polyinosinic-polycytidylic acid [poly(I:C)], an analog of viral double-stranded RNA, induces the secretion of cytokines and chemokines from cultured corneal fibroblasts. We have now investigated the role of nuclear factor (NF)-κB and phosphoinositide 3-kinase (PI3K) signaling pathways in poly(I:C)-induced cytokine and chemokine secretion from corneal fibroblasts.
Materials and Methods: Human corneal fibroblasts were cultured with poly(I:C) in the absence or presence of IKK-2 inhibitor or LY294002, which are inhibitors of NF-κB and PI3K signaling, respectively. The release of the pro-inflammatory cytokine interleukin (IL)-6 and the chemokines IL-8, IP-10, and RANTES from the cells was measured with an enzyme-linked immunosorbent assay.
Results: Poly(I:C) induced the secretion of IL-6, IL-8, IP-10, and RANTES from corneal fibroblasts. Whereas the poly(I:C)-induced secretion of IL-6, IP-10, and RANTES was inhibited by both IKK-2 inhibitor and LY294002, that of IL-8 was blocked only by IKK-2 inhibitor.
Conclusions: The poly(I:C)-induced secretion of IL-6, IP-10, and RANTES from human corneal fibroblasts is mediated by both NF-κB and PI3K signaling pathways, whereas that of IL-8 is mediated by the NF-κB pathway. These signaling pathways thus likely contribute to local inflammation in the corneal stroma induced by viral infection.
ACKNOWLEDGMENTS
The authors thank Eriko Yamanaga, Shizuka Murata, Yukari Mizuno, and the staff of Yamaguchi University Center for Gene Research for technical assistance.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.