Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
J Cell Biochem. 2010 Sep 1;111(1):40-8. doi: 10.1002/jcb.22648.
Periodontitis is a chronic bacterial infection of tooth-supporting structures. T-helper type 1 (Th1) cells are related to the exacerbation of periodontal disease. Human gingival fibroblasts (HGFs), the major cell type in periodontal connective tissues, are involved in immunological response in periodontal tissues. However, it is uncertain whether HGFs are related to Th1 response. Chemokine (C-X-C motif) ligand 10 (CXCL10) is a cytokine, that is related to Th1 cells migration. Intercellular adhesion molecule (ICAM)-1 is involved in Th1 cells retention and activation in inflamed tissue. The aim of this study is to examine the effect of oncostatin M (OSM) on CXCL10 and ICAM-1 expression in HGFs. OSM stimulation induced CXCL10 and ICAM-1 expression in HGFs. Moreover, the synergistic effects of CXCL10 release and ICAM-1 expression in HGFs were observed with combined stimulation of interleukin (IL)-1beta and OSM. OSM increased type 1 IL-1 receptor (IL-1R1) expression, and IL-1beta enhanced OSMRbeta expression on HGFs. IL-1beta + OSM stimulation enhanced the phosphorylation of inhibitor of nuclear factor kappaB (IkappaB)-alpha, signal transducer and activator of transcription (STAT)3, c-Jun N terminal kinase (JNK), and protein kinase B (Akt) compared to OSM or IL-1beta stimulation. CXCL10 production from OSM + IL-1beta stimulated HGFs was suppressed by nuclear factor (NF)-kappaB, STAT3, JNK, and phosphoinositide-3-kinase (PI3K) inhibitors. On the other hand, only NF-kappaB and STAT3 inhibitors suppressed ICAM-1 expression enhanced by OSM + IL-1beta treatment. These effects of OSM and IL-1beta may promote Th1 cells infiltration and retention in periodontally diseased tissues and be related to exacerbation of periodontal disease.
牙周炎是一种牙齿支持结构的慢性细菌性感染。辅助性 T 细胞 1（Th1）细胞与牙周病的恶化有关。人牙龈成纤维细胞（HGFs）是牙周组织中主要的细胞类型，参与牙周组织的免疫反应。然而，HGFs 是否与 Th1 反应有关尚不确定。趋化因子（C-X-C 基序）配体 10（CXCL10）是一种细胞因子，与 Th1 细胞的迁移有关。细胞间黏附分子（ICAM）-1 参与 Th1 细胞在炎症组织中的保留和激活。本研究旨在研究oncostatin M（OSM）对 HGFs 中 CXCL10 和 ICAM-1 表达的影响。OSM 刺激诱导 HGFs 中 CXCL10 和 ICAM-1 的表达。此外，在白细胞介素（IL）-1β和 OSM 的联合刺激下，观察到 HGFs 中 CXCL10 释放和 ICAM-1 表达的协同作用。OSM 增加了 1 型白细胞介素 1 受体（IL-1R1）的表达，IL-1β增强了 HGFs 上的 OSMRβ表达。与 OSM 或 IL-1β刺激相比，IL-1β+OSM 刺激增强了核因子 kappaB（NF-κB）、信号转导和转录激活因子（STAT）3、c-Jun N 末端激酶（JNK）和蛋白激酶 B（Akt）的磷酸化。来自 OSM+IL-1β刺激的 HGFs 的 CXCL10 产生被核因子（NF）-κB、STAT3、JNK 和磷脂酰肌醇 3-激酶（PI3K）抑制剂抑制。另一方面，只有 NF-κB 和 STAT3 抑制剂抑制了 OSM+IL-1β 处理增强的 ICAM-1 表达。OSM 和 IL-1β 的这些作用可能促进 Th1 细胞在牙周病组织中的浸润和保留，并与牙周病的恶化有关。
