Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266003, China.
Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266003, China.
Exp Eye Res. 2018 Feb;167:152-162. doi: 10.1016/j.exer.2016.11.017. Epub 2016 Nov 24.
Pentraxin3 (PTX3), a member of long pentraxin family, plays a non-redundant role in human humoral innate immunity. However, whether PTX3 is expressed by corneal epithelial cells and its role during corneal fungi infection has not yet been investigated. To identify the presence of PTX3 in cornea, the possible mechanisms involved in its expression, and also the effects on corneal anti-fungi innate immune response, clinic human corneal tissues and cultured human corneal epithelial cells (HCECs) were resorted. PTX3 mRNA and protein were detected in corneal samples and cultured HCECs, which was significantly up-regulated after exposing to Aspergillus fumigatus (A. fumigatus). Pretreated with specific inhibitors, only Syk contributed to the regulation of PTX3 expression in Dectin-1/Syk signal axis. Furthermore, among the MAPK members (p38 MAPK, ERK1/2 and JNK), only ERK1/2 and JNK were responsible for A. fumigatus induced PTX3 production. Blocking of endogenous PTX3 by siRNA down-regulated the production of IL-1β at both mRNA and protein levels. Meanwhile, blocking of PTX3 also inhibited the phosphorylation of ERK1/2 and JNK, but not p38 MAPK. These findings demonstrate that PTX3 is expressed in human corneal epithelial cells and Syk, ERK1/2, JNK signaling pathways play an important role in the regulation of PTX3 induction. PTX3 plays a proinflammatory role in corneal epithelial anti-fungi immune response by affecting the production of IL-1β and activation of some proinflammatory signaling pathways (ERK1/2 and JNK).
五聚素 3（PTX3）是长五聚素家族的成员，在人类体液先天免疫中发挥着不可或缺的作用。然而，角膜上皮细胞是否表达 PTX3 及其在角膜真菌感染中的作用尚未得到研究。为了确定 PTX3 是否存在于角膜中，以及其表达的可能机制，以及对角膜抗真菌先天免疫反应的影响，本研究采用临床人角膜组织和培养的人角膜上皮细胞（HCEC）。在角膜样本和培养的 HCEC 中检测到 PTX3 mRNA 和蛋白，在暴露于烟曲霉（A. fumigatus）后显著上调。用特异性抑制剂预处理后，只有 Syk 在 Dectin-1/Syk 信号轴中对 PTX3 表达的调节有贡献。此外，在 MAPK 成员（p38 MAPK、ERK1/2 和 JNK）中，只有 ERK1/2 和 JNK 负责 A. fumigatus 诱导的 PTX3 产生。用 siRNA 阻断内源性 PTX3 下调了 IL-1β 在 mRNA 和蛋白水平的产生。同时，阻断 PTX3 也抑制了 ERK1/2 和 JNK 的磷酸化，但不抑制 p38 MAPK。这些发现表明，PTX3 在人角膜上皮细胞中表达，Syk、ERK1/2、JNK 信号通路在 PTX3 诱导的调节中发挥重要作用。PTX3 通过影响 IL-1β 的产生和某些促炎信号通路（ERK1/2 和 JNK）的激活，在角膜上皮细胞抗真菌免疫反应中发挥促炎作用。
