Fujitsu Youichiro, Fukuda Ken, Kumagai Naoki, Nishida Teruo
Department of Biomolecular Recognition and Ophthalmology, Yamaguchi University School of Medicine, Ube City, Yamaguchi, Japan.
Exp Eye Res. 2003 Jan;76(1):107-14. doi: 10.1016/s0014-4835(02)00248-8.
Giant papillae, characteristic lesions of vernal keratoconjunctivitis, are formed as a result of the proliferation of conjunctival fibroblasts, the deposition of extracellular matrix, and the infiltration of inflammatory cells. The concentration of interleukin (IL)-4 is also increased in the tear fluid of individuals with ocular allergic diseases. The possible role of IL-4 in the development of giant papillae was investigated by examining the effects of this cytokine on cultured human conjunctival fibroblasts. Reverse transcription and polymerase chain reaction analysis revealed the presence of transcripts encoding the IL-4 receptor alpha chain in these cells, and flow cytometry demonstrated the expression of this protein on the cell surface. IL-4 induced the proliferation of conjunctival fibroblasts in a concentration-dependent manner, and this effect was inhibited by neutralizing antibodies to the IL-4 receptor. Enzyme immunoassays revealed that IL-4 also increased in a concentration-dependent manner the amounts of procollagen type I C-peptide and fibronectin released into the culture supernatant by conjunctival fibroblasts. A whole-cell enzyme-linked immunosorbent assay showed that IL-4 increased the deposition of collagen type III by conjunctival fibroblasts. Furthermore, reverse transcription combined with real-time polymerase chain reaction analysis revealed that IL-4 increased the abundance of collagen type III mRNA in these cells. These results demonstrate that human conjunctival fibroblasts express receptors for IL-4, and that IL-4 stimulates both the proliferation of and the production of extracellular matrix proteins by these cells. These effects of IL-4 might contribute to the formation of giant papillae in individuals with vernal keratoconjunctivitis.
巨大乳头是春季角结膜炎的特征性病变，它是由结膜成纤维细胞增殖、细胞外基质沉积以及炎性细胞浸润形成的。眼部过敏性疾病患者的泪液中白细胞介素（IL）-4的浓度也会升高。通过检测这种细胞因子对培养的人结膜成纤维细胞的影响，研究了IL-4在巨大乳头形成过程中的可能作用。逆转录和聚合酶链反应分析显示这些细胞中存在编码IL-4受体α链的转录本，流式细胞术证明该蛋白在细胞表面表达。IL-4以浓度依赖的方式诱导结膜成纤维细胞增殖，并且这种作用被抗IL-4受体的中和抗体所抑制。酶免疫测定显示，IL-4还以浓度依赖的方式增加了结膜成纤维细胞释放到培养上清液中的I型前胶原C肽和纤连蛋白的量。全细胞酶联免疫吸附测定表明，IL-4增加了结膜成纤维细胞III型胶原的沉积。此外，逆转录结合实时聚合酶链反应分析显示IL-4增加了这些细胞中III型胶原mRNA的丰度。这些结果表明，人结膜成纤维细胞表达IL-4受体，并且IL-4刺激这些细胞的增殖以及细胞外基质蛋白的产生。IL-4的这些作用可能有助于春季角结膜炎患者巨大乳头的形成。
