IGA ANTIBODIES AND PERIODONTAL INFLAMMATION

此R 01应用程序的目标是阐明 免疫球蛋白A（伊加）在人类牙周病， 随着年龄的增长，许多成年人受到折磨， 老年人牙齿脱落的主要原因。 的最新进展 了解伊加的生理作用表明，它的功能 作为免疫过程的非炎症调节剂。 是 假设循环（血清）伊加抗体， 与IgG抗体相反，对炎症的抑制作用 牙龈单核吞噬细胞对脂多糖的反应 (LPS)和其他牙周病原体抗原，特别是 牙龈卟啉单胞菌（Pg）。 牙龈单核吞噬细胞 外周血单核细胞将用Pg LPS刺激， Pg LPS的伊加或IgG抗体的存在，及其 将根据以下方面评估答复： 炎性细胞因子，白介素-1（IL-1），白介素-6（IL-6）， 和肿瘤坏死因子-α（TNF-α），以及IL-1受体 拮抗剂 这些分子分泌到培养液中， 用免疫化学方法测量它们的细胞内表达 将根据信使RNA的转录来确定。 假设的机制和条件 抑制炎性细胞因子产生的发生将是 研究了 进一步假设Pg的伊加抗体 LPS和其他抗原下调抗原呈递细胞 牙龈单核吞噬细胞和B活性 淋巴细胞，这是负责永久免疫 对牙周病原体的反应。 据推测， 失调的反应有助于慢性 破坏性炎症，而不是消除病原体。 的 IgA介导的抗原提呈功能的调节 牙龈单核吞噬细胞、血液单核细胞和B 淋巴细胞将根据以下表达进行评估： 重要的“第二信号”表面分子（B7.1、B7.2和CD$）） 通过这些细胞与T淋巴细胞在初级 和继发性免疫反应。 T细胞的反应能力 这些细胞在伊加的影响下呈递Pg抗原 还将测定抗体。 如果发现伊加抗体， 对炎症反应有改善作用， 免疫反应的永久化，然后采取措施， 血清伊加抗体对牙周病原体的反应可能 构成一种新的治疗方法。

The objectives of this R01 application are to elucidate the role of immunoglobulin A (IgA) in human periodontal disease, which afflicts significant numbers of adults with increasing age, and is a major cause of tooth loss in the elderly. Recent advances in understanding the physiological role of IgA suggest that it functions as a non-inflammatory regulator of immune processes. It is hypothesized that circulating (serum) IgA antibodies have, in contrast to IgG antibodies, a suppressive effect on the inflammatory responses of gingival mononuclear phagocytes to lipopolysaccharide (LPS) and other antigens of periodontal pathogens, especially Porphyromonas gingivalis (Pg). Gingival mononuclear phagocytes and peripheral blood monocytes will be stimulated with Pg LPS in the presence of IgA or IgG antibodies to Pg LPS, and their responses will be assessed in terms of the production of inflammatory cytokines, interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor-necrosis factor-alpha (TNF-alpha), and of IL-1 receptor antagonist. Secretion of these molecules into the culture fluid will be measured immunochemically, and their intracellular expression will be determined in terms of the transcription of messenger RNA. The mechanisms and conditions under which the postulated suppression of inflammatory cytokine production occurs will be investigated. It is further hypothesized that IgA antibodies to Pg LPS and other antigens down-regulate the antigen-presenting cell activities of both gingival mononuclear phagocytes and B lymphocytes, which are responsible for the perpetuation of immune responses to periodontal pathogens. It is postulated that such dysregulated responses contribute to the continuation of chronic destructive inflammation, instead of eliminating the pathogens. The IgA-mediated modulating on the antigen-presenting capabilities of gingival mononuclear phagocytes, blood monocytes, and B lymphocytes will be assessed in terms of the expression of important 'second signal' surface molecules (B7.1, B7.2, and CD$)) by which thee cells communicate with T lymphocytes in primary and secondary immune responses. The ability of T cells to respond to Pg antigens presented by these cells under the influence of IgA antibodies will also be determined. If IgA antibodies are found to have ameliorating effects on inflammatory responses and the perpetuation of immune responses, then measures to enhance the serum IgA antibody response to periodontal pathogens might constitute a novel therapeutic approach.