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Keitaro Mashimo, Ayumi Usui, Nobuyuki Ebihara; The role of Oncostatin M in the pathogenesis of severe allergic conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5753.
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© ARVO (1962-2015); The Authors (2016-present)
Vernal Keratoconjunctivitis (VKC) is severe allergic conjunctivitis. In the conjunctival giant papillae of VKC, many inflammatory cells infiltrate and produce various cytokine and chemokine. However, to date, there are no reports that which cytokine has a crucial role in the giant papillae formation of VKC. Oncostatin M (OSM) is IL-6 family. OSM signals through the receptor, stimulates the JAK/STAT signal pathways. OSM has multiple functions such as inflammation, proliferation, remodeling, fibrosis, apoptosis and more. The purpose of this study is to investigate the role of OSM in the pathogenesis of VKC.
The primary human conjunctival epithelial cells (HConEpiCs) and human conjunctival fibroblasts (HConFs) were cultured. Expression of OSM receptor (OSMR) in HConEpiCs and HConFs was assessed by flow cytometry and immunocytochemistry. We estimated the intensity of expression in OSMR of HConEpiCs treated with IL-4, IL-13, TGFβ and TNFα ,using flow cytometry. We investigated OSM induced STAT1 and STAT3 phosphorylation in HConEpiCs by western blotting. We also analyzed the comprehensive gene expression following OSM treatment in HConEpiCs and HConFs by microarray and real-time PCR. And we measured the concentration of OSM in the tears of seven VKC patients using ELISA. The expression of OSM in giant papillae of VKC patients was determined by immunohistochemistry and real-time PCR.
OSMR was expressed in HConEpiCs and HConFs. However, OSMR was not upregulated with IL-4, IL-13, TGFβ and TNFα. Phosoho-STAT1 and 3 were increased in HConEpiCs treated with OSM. The mRNA of Matrix metallopeptidase (MMP)1, MMP3, Suppressor of cytokine signaling 3 (SOCS3), Serpin peptidase inhibitor, clade B (SERPINB3), IL-20, IL-24 and Tenascin C were upregulated in HConEpiCs treated with OSM.(p<0.05) Meanwhile, in HConFs, mRNA of SOCS3, SERPINB3, IL-33 and Vascular endothelial growth factor (VEGF) were upregulated by OSM.(p<0.05) Concentrations of OSM in the tears of VKC patients were increased. Many infiltrating cells in giant papillae produced OSM.
OSM may contribute to inflammation and tissue remodeling in giant papillae of VKC patients.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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