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Zai-Long Chi, Fan Lu, Jia Qu; The role of calprotectin in uveitis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):523.
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© ARVO (1962-2015); The Authors (2016-present)
Uveitis and its sequelae remain an important cause of blindness worldwide. Acute anterior uveitis (AAU) is generally recognized as the most common form of uveitis. Calprotectin (also known as heterodimers of S100A8/S100A9) is a calcium-binding protein which mainly expresses in myeloid cells and plays a prominent role in the regulation of inflammatory processes and immune response. To date, there have been few studies on this protein and uveitis, and the extracellular function of this protein in AAU remains unclear. Here, we report the role of calprotectin in endotoxin-induced uveitis (EIU) rat model and patients with uveitis.
All animal experiments were conducted in compliance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. All patients involved in this study were treated according to the tenets of the Declaration of Helsinki and was approved by the Clinical Research Ethics Committee of institutions. LPS (lipopolisaccaride) was injected intraperitoneally in male rats to produce anterior uveitis and keratitis. DEX (Dexamethasone) and BAY 11-7085 (an inhibitor of I-kB phosphorylation) was injected intraperitoneally. Serum samples were collected from different types of uveitis patients. The mRNAs and protein levels were measured by real-time PCR, flow cytometry, Immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA).
In rat models of EIU, S100A8 and S100A9-positive granulocytes and monocytes increased significantly in the iris-ciliary body and cornea as well as in the blood. Interestingly, Glucocorticoids slightly increased S100A8 and S100A9 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 and S100A9 levels in leukocytes and the iris-ciliary body after LPS administration. Additionally, S100A8 and S100A9 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.
Calprotectin plays a pivotal role in the processes of AAU through involvement in migration and infiltration of S100A8 and S100A9-positive cells. Our findings suggest that serum levels of calprotectin protein can be used to monitor inflammatory activity in AAU.
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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