Fujihashi K, Beagley K W, Kono Y, Aicher W K, Yamamoto M, DiFabio S, Xu-Amano J, McGhee J R, Kiyono H
Department of Oral Biology, University of Alabama, Birmingham 35294.
Am J Pathol. 1993 Apr;142(4):1239-50.
A unique characteristic of the localized inflammatory tissue in the periodontium (e.g., adult periodontitis [AP]) is the accumulation of IgG (IgG1 > IgG2 > IgG3 > or = IgG4) followed by IgA plasma cells (IgA1 > IgA2). However, the exact molecular mechanisms contributing to these elevated B-cell responses at the local disease site are still unknown. Thus, this study has examined the production of cytokines of importance in B-cell responses, e.g., interleukin (IL)-2, IL-4, IL-5, and IL-6 by gingival mononuclear cells (GMC) isolated from patients in severe stages of AP. These cytokines were assessed at the protein and messenger (m)RNA levels to understand their importance for the observed increased B-cell responses present in these tissues. Among the four cytokines tested by respective cytokine-specific, polymerase chain reaction and dot-blot hybridization, high levels of IL-5- and IL-6-specific mRNA were noted in GMC freshly isolated from AP patients. On the other hand, specific message for IL-2 and IL-4 were not present. Further, the analysis of culture supernatants of GMC also revealed that cells from AP patients spontaneously produced IL-5 and IL-6 but not IL-2 and IL-4. In contrast, when peripheral blood mononuclear cells isolated from the same patients were examined for these cytokines, no detectable levels of mRNA or secreted cytokines were noted. These results showed that GMC from localized inflammatory tissues in severe stages of AP possess a distinct cytokine profile represented by high levels of IL-5 and IL-6 mRNA expression and protein synthesis, whereas IL-2 and IL-4 were not detected. Further, this study supports the concept that AP is a localized inflammatory disease, because GMC from the inflamed tissue actively produce IL-5 and IL-6, whereas peripheral blood mononuclear cells from the same patients do not.
牙周组织局部炎症(如成人牙周炎[AP])的一个独特特征是IgG(IgG1>IgG2>IgG3>或=IgG4)随后是IgA浆细胞(IgA1>IgA2)的积累。然而,导致局部疾病部位这些B细胞反应升高的确切分子机制仍不清楚。因此,本研究检测了从AP严重阶段患者分离的牙龈单核细胞(GMC)中对B细胞反应重要的细胞因子的产生,例如白细胞介素(IL)-2、IL-4、IL-5和IL-6。在蛋白质和信使(m)RNA水平评估这些细胞因子,以了解它们对这些组织中观察到的B细胞反应增加的重要性。在所测试的四种细胞因子中,通过各自的细胞因子特异性聚合酶链反应和斑点杂交,在从AP患者新鲜分离的GMC中发现高水平的IL-5和IL-6特异性mRNA。另一方面,未检测到IL-2和IL-4的特异性信息。此外,对GMC培养上清液的分析还表明,AP患者的细胞自发产生IL-5和IL-6,但不产生IL-2和IL-4。相反,当检测从同一患者分离的外周血单核细胞中的这些细胞因子时,未检测到mRNA或分泌细胞因子的可检测水平。这些结果表明,AP严重阶段局部炎症组织中的GMC具有以高水平IL-5和IL-6 mRNA表达及蛋白质合成代表的独特细胞因子谱,而未检测到IL-2和IL-4。此外,本研究支持AP是一种局部炎症性疾病的概念,因为来自炎症组织的GMC积极产生IL-5和IL-6,而同一患者的外周血单核细胞则不产生。