Abstract

Uveitis, the pathologic condition of inflammation of the uvea, frequently leads to severe vision loss and blindness. S100A8 is a calcium-binding protein which mainly expresses in granulocytes and monocytes and plays a prominent role in the regulation of inflammatory processes and immune response. Here, we determined the role of S100A8-positive cells in acute anterior uveitis (AAU) and keratitis. In rat models of endotoxin (lipopolisaccharide, LPS) -induced uveitis (EIU) and keratitis, S100A8-positive granulocytes and monocytes increased significantly in the iris-ciliary body and cornea as well as in the blood. Interestingly, Glucocorticoids slightly increased S100A8 levels in leukocytes, but reduced its presence significantly in the iris-ciliary body after LPS injection. Moreover, inhibition of NF-kB activation remarkably suppressed both progression of AAU and total S100A8 levels in leukocytes and the iris-ciliary body after LPS administration. Additionally, S100A8 protein level was also found to be elevated in the serum of AAU patients parallel with the progression of AAU through the designated clinical stages. Thus, S100A8 plays a pivotal role in the processes of AAU through involvement in migration and infiltration of S100A8-positive cells. Our findings suggest that serum levels of S100A8 protein can be used to monitor inflammatory activity in AAU.

Highlights

  • Uveitis, the pathologic condition of inflammation of the uvea, frequently leads to severe vision loss and blindness

  • S100A8 is specific for cells of myeloid origin such as granulocytes, monocytes, and macrophages, but it is not detected in resident tissue macrophages[1,2,3,4,5,6]

  • After LPS injection, percentages of S100A8-positive granulocytes increased at 9 hours, reached a maximum (25.7 ± 2.2%) at 12 hours, and decreased (Fig. 2C), whereas in contrast, percentages of S100A8-positive monocytes increased to 23–29% at 12–36 hours after LPS

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Summary

Introduction

The pathologic condition of inflammation of the uvea, frequently leads to severe vision loss and blindness. In rat models of endotoxin (lipopolisaccharide, LPS) -induced uveitis (EIU) and keratitis, S100A8-positive granulocytes and monocytes increased significantly in the iris-ciliary body and cornea as well as in the blood. Walscheid et al.[27] found that among juvenile idiopathic arthritis-associated uveitis (JIAU) patients with autoimmune uveitis (a common chronic anterior uveitis), S100A8/A9 and S100A12 levels were increased in the serum and aqueous humor. These serum levels reflect activity of joint and eye disease. Systemic injection of LPS induces bilateral acute ocular inflammation in susceptible strains of rats and mice, which is an animal model for human AAU29. Our findings suggest that S100A8 is involved in the pathological inflammation of EIU and keratitis, and that measuring S100A8 levels can be a useful method to monitor inflammatory activity in AAU

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