Dongari-Bagtzoglou A I, Ebersole J L
Department of Periodontics, University of Texas, Health Science Center at San Antonio, USA.
J Periodontol. 1996 Sep;67(9):871-8. doi: 10.1902/jop.1996.67.9.871.
Within the in vivo environment human gingival fibroblasts (HGF) may be challenged with bacteria or bacterial products. This interaction may result in the release of cytokines which are directly or indirectly involved in connective tissue and bone catabolism, such as interleukin (IL)-1 beta, IL-6, and IL-8. Our investigation has tested the hypothesis that HGF from Actinobacillus actinomycetemcomitans (Aa)-infected patients with rapidly destructive forms of periodontitis, such as localized juvenile periodontitis (LJP), respond to Aa challenge with an exaggerated secretion of IL-1 beta, IL-6, and IL-8. We have compared the in vitro profiles of these cytokines by Aa-challenged HGF obtained from 2 healthy subjects, 2 Aa-infected, slowly progressing adult periodontitis (AP) patients and 2 LJP patients. HGF were challenged throughout a 48-hour period with formalinized whole bacterial cells, and culture supernatants were analyzed for cytokine content using RIA. No differences were noted in the IL-1 beta secretion levels among the different HGF cultures. Although basal (unchallenged) IL-6 and IL-8 production was similar in all HGF cultures, HGF from the two LJP patients responded to Aa challenge with a more rapid IL-6 and a more pronounced IL-8 secretion than healthy or AP HGF. We also tested the ability of human serum antibodies against Aa to moderate the Aa-elicited HGF cytokine secretion by adding human serum, with normal or elevated antibody content. Both sera appeared to have an upregulating effect on IL-6 and IL-8 secretion. Depletion of 95% of the anti-Aa antibody from serum by absorption did not affect its activity. Based on the response of HGF from two LJP patients, we propose that Aa-induced pathology in LJP may be modulated by stimulation of rapid and/or exaggerated secretion of cytokines with potential catabolic effects, although studies with a larger group of LJP patients are needed to further test this hypothesis. Furthermore, serum antibodies against this microorganism do not appear to have a neutralizing effect in cytokine-eliciting HGF-Aa interactions.
在体内环境中，人牙龈成纤维细胞（HGF）可能会受到细菌或细菌产物的刺激。这种相互作用可能导致细胞因子的释放，这些细胞因子直接或间接参与结缔组织和骨分解代谢，如白细胞介素（IL）-1β、IL-6和IL-8。我们的研究检验了这样一个假设：来自感染伴放线放线杆菌（Aa）的快速破坏性牙周炎患者（如局限性青少年牙周炎（LJP））的HGF，对Aa刺激会过度分泌IL-1β、IL-6和IL-8。我们比较了从2名健康受试者、2名感染Aa的缓慢进展性成人牙周炎（AP）患者和2名LJP患者获得的经Aa刺激的HGF的这些细胞因子的体外谱。用甲醛固定的全菌细胞对HGF进行48小时的刺激，并用放射免疫分析法（RIA）分析培养上清液中的细胞因子含量。不同HGF培养物中IL-1β分泌水平没有差异。虽然所有HGF培养物中基础（未刺激）的IL-6和IL-8产生相似，但两名LJP患者的HGF对Aa刺激的反应是IL-6分泌更快，IL-8分泌比健康或AP的HGF更明显。我们还通过添加抗体含量正常或升高的人血清，测试了人抗Aa血清抗体调节Aa诱导的HGF细胞因子分泌的能力。两种血清似乎都对IL-6和IL-8分泌有上调作用。通过吸收从血清中去除95%的抗Aa抗体并不影响其活性。基于两名LJP患者的HGF的反应，我们提出，LJP中Aa诱导的病理可能通过刺激具有潜在分解代谢作用的细胞因子的快速和/或过度分泌来调节，尽管需要对更多LJP患者进行研究以进一步验证这一假设。此外，针对这种微生物的血清抗体在引发细胞因子的HGF-Aa相互作用中似乎没有中和作用。
