Chi Zai-Long, Hayasaka Yoriko, Zhang Xue-Yun, Cui Hu-Shan, Hayasaka Seiji
Department of Ophthalmology, Graduate School of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Exp Eye Res. 2007 Feb;84(2):254-65. doi: 10.1016/j.exer.2006.09.016. Epub 2006 Nov 13.
S100A9 is a pro-inflammatory protein expressed in infiltrating granulocytes and monocytes. We determined role of S100A9 in endotoxin (LPS)-induced uveitis (EIU) and keratitis in Wistar rats. Anti-S100A9 antibody decreased partially clinical scores, protein, and cells in the aqueous humor at 18-36 h, compared with the LPS group. S100A9-positive cells were expressed in the iris-ciliary body (ICB) and cornea at 24-48 h. Activated caspase-3 (related to apoptosis) and S100A9 co-expressed in ICB at 18-48 h after LPS injection. S100A9 was not expressed in ED2-positive cells in ICB. Dexamethasone (DEX) increased S100A9 mRNA and protein levels in the circulating blood leukocytes, but reduced S100A9 mRNA and protein levels in ICB after LPS injection. BAY 11-7085 (an inhibitor of I-kappaB phosphorylation) suppressed S100A9 mRNA in leukocytes (43.5%) and ICB (68.5%), respectively, after LPS injection. It is possible that S100A9-positive granulocytes and monocyte/macrophages may play a role in the late phase of EIU and keratitis that DEX may inhibit the migration of S100A9-positive granulocytes and monocytes from the blood into the extravascular tissues, and that nuclear factor (NF)-kappaB pathway may be involved in S100A9 expression. S100A9 could play a role in the clearance of inflammatory cells at the late phase of EIU.
S100A9是一种在浸润的粒细胞和单核细胞中表达的促炎蛋白。我们确定了S100A9在Wistar大鼠内毒素（LPS）诱导的葡萄膜炎（EIU）和角膜炎中的作用。与LPS组相比，抗S100A9抗体在18 - 36小时部分降低了临床评分、房水中的蛋白质和细胞。S100A9阳性细胞在24 - 48小时在虹膜睫状体（ICB）和角膜中表达。LPS注射后18 - 48小时，活化的半胱天冬酶-3（与凋亡相关）和S100A9在ICB中共表达。S100A9在ICB中的ED2阳性细胞中不表达。地塞米松（DEX）增加了循环血白细胞中S100A9的mRNA和蛋白水平，但降低了LPS注射后ICB中S100A9的mRNA和蛋白水平。BAY 11 - 7085（一种I-κB磷酸化抑制剂）分别在LPS注射后抑制了白细胞（43.5%）和ICB（68.5%）中S100A9的mRNA。S100A9阳性粒细胞和单核细胞/巨噬细胞可能在EIU和角膜炎的后期发挥作用，DEX可能抑制S100A9阳性粒细胞和单核细胞从血液向血管外组织的迁移，并且核因子（NF）-κB通路可能参与S100A9的表达。S100A9可能在EIU后期的炎症细胞清除中发挥作用。
