Izuhara Kenji, Nunomura Satoshi, Nanri Yasuhiro, Ogawa Masahiro, Ono Junya, Mitamura Yasutaka, Yoshihara Tomohito
Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, 5-1-1, Nabeshima, Saga, 849-8501, Japan.
Shino-Test Corporation, 2-29-14, Oonodai, Sagamihara, 229-0011, Japan.
Cell Mol Life Sci. 2017 Dec;74(23):4293-4303. doi: 10.1007/s00018-017-2648-0. Epub 2017 Sep 8.
We found for the first time that IL-4 and IL-13, signature type 2 cytokines, are able to induce periostin expression. We and others have subsequently shown that periostin is highly expressed in chronic inflammatory diseases-asthma, atopic dermatitis, eosinophilc chronic sinusitis/chronic rhinosinusitis with nasal polyp, and allergic conjunctivitis-and that periostin plays important roles in the pathogenesis of these diseases. The epithelial/mesenchymal interaction via periostin is important for the onset of allergic inflammation, in which periostin derived from fibroblasts acts on epithelial cells or fibroblasts, activating their NF-κB. Moreover, the immune cell/non-immune cell interaction via periostin may be also involved. Now the significance of periostin has been expanded into other inflammatory or fibrotic diseases such as scleroderma and pulmonary fibrosis. The cross-talk of periostin with TGF-β or pro-inflammatory cytokines is important for the underlying mechanism of these diseases. Because of its pathogenic importance and broad expression, diagnostics or therapeutic drugs can be potentially developed to target periostin as a means of treating these diseases.
我们首次发现,标志性的2型细胞因子白细胞介素-4和白细胞介素-13能够诱导骨膜蛋白的表达。随后,我们和其他研究人员表明,骨膜蛋白在慢性炎症性疾病(如哮喘、特应性皮炎、嗜酸性粒细胞性慢性鼻窦炎/伴鼻息肉的慢性鼻-鼻窦炎和过敏性结膜炎)中高度表达,并且骨膜蛋白在这些疾病的发病机制中发挥重要作用。通过骨膜蛋白介导的上皮/间充质相互作用对于过敏性炎症的发生很重要,其中成纤维细胞来源的骨膜蛋白作用于上皮细胞或成纤维细胞,激活它们的核因子κB。此外,通过骨膜蛋白介导的免疫细胞/非免疫细胞相互作用可能也参与其中。现在,骨膜蛋白的重要性已扩展到其他炎症性或纤维化疾病,如硬皮病和肺纤维化。骨膜蛋白与转化生长因子-β或促炎细胞因子之间的相互作用对于这些疾病的潜在机制很重要。由于其致病重要性和广泛表达,有可能开发针对骨膜蛋白的诊断方法或治疗药物,作为治疗这些疾病的一种手段。