Ozawa Akiko, Tada Hiroyuki, Tamai Riyoko, Uehara Akiko, Watanabe Kouichi, Yamaguchi Takahiro, Shimauchi Hidetoshi, Takada Haruhiko, Sugawara Shunji
Department of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
J Leukoc Biol. 2003 Sep;74(3):352-9. doi: 10.1189/jlb.0103044.
To investigate the role of human gingival fibroblasts (HGF), the major constituents of gingival tissue in periodontal inflammatory disease, the expression of interleukin-2 receptor (IL-2R) alpha, beta, and gamma chains was examined. Immunohistochemistry showed a pronounced accumulation of CD8(+) T cells in the inflamed lamina propria of gingival tissue from patients with adult periodontitis. HGF express IL-2Rbeta and IL-2Rgamma at mRNA and protein levels, but the expression of IL-2Ralpha could not be detected, as assessed by reverse transcriptase-polymerase chain reaction and flow cytometry. IL-2Rbeta, and -gamma expressed on HGF were functionally active, as addition of neutralizing anti-IL-2Rbeta and -gamma antibodies caused inhibition of the IL-2-induced production of monocyte chemoattractant protein-1 (MCP-1), and addition of IL-2 induced phosphorylation of Janus tyrosine kinase 3, which is critical in signaling through IL-2Rgamma in HGF. The IL-2-induced MCP-1 production was significantly inhibited by pretreatment with neutralizing antibody to IL-15. Addition of IL-2 also induced a marked up-regulation of the expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of HGF, which in turn, significantly augmented the adhesion of human neutrophils, which were inhibited by an anti-ICAM-1 antibody. These results suggest that HGF express functional IL-2Rbetagamma, respond to IL-2 from infiltrated T cells, and actively participate in the inflammatory process in the periodontal region and that IL-15 produced by HGF sustains IL-2-mediated signaling in HGF.
为了研究人牙龈成纤维细胞（HGF）在牙周炎症性疾病牙龈组织主要成分中的作用，检测了白细胞介素-2受体（IL-2R）α、β和γ链的表达。免疫组织化学显示，在成人牙周炎患者牙龈组织炎症固有层中CD8(+) T细胞明显聚集。通过逆转录聚合酶链反应和流式细胞术评估，HGF在mRNA和蛋白质水平表达IL-2Rβ和IL-2Rγ，但未检测到IL-2Rα的表达。HGF上表达的IL-2Rβ和-γ具有功能活性，因为添加中和性抗IL-2Rβ和-γ抗体可抑制IL-2诱导的单核细胞趋化蛋白-1（MCP-1）的产生，添加IL-2可诱导Janus酪氨酸激酶3的磷酸化，这在HGF中通过IL-2Rγ信号传导中起关键作用。用抗IL-15中和抗体预处理可显著抑制IL-2诱导的MCP-1产生。添加IL-2还可诱导HGF表面细胞间黏附分子-1（ICAM-1）表达明显上调，这反过来又显著增强了人中性粒细胞的黏附，而抗ICAM-1抗体可抑制这种黏附。这些结果表明，HGF表达功能性IL-2Rβγ，对浸润T细胞产生的IL-2作出反应，并积极参与牙周区域的炎症过程，并且HGF产生的IL-15维持HGF中IL-2介导的信号传导。
