IGA ANTIBODIES AND PERIODONTAL INFLAMMATION

本R01申请的目的是阐明 免疫球蛋白A(IgA)在牙周病中的作用 随着年龄的增长，相当数量的成年人会受到折磨，是一种 老年人牙齿脱落的主要原因。的最新进展 了解免疫球蛋白A的生理作用表明它的功能 作为免疫过程的非炎症性调节因子。它是 假设循环(血清)IgA抗体有 与免疫球蛋白抗体相比，它对炎症有抑制作用。 牙龈单核巨噬细胞对内毒素的反应性 (LPs)和其他牙周病原体抗原，尤其是 牙龈卟啉单胞菌(Pg)。牙龈单核巨噬细胞 外周血单核细胞可被PG-内毒素刺激 Pg-内毒素IgA或Ig G抗体的存在及其临床意义 答复将根据以下方面进行评估 炎症细胞因子、白介素1(IL-1)、白介素6(IL-6)、 和肿瘤坏死因子-α(TNF-α)和IL-1受体 对抗者。将这些分子分泌到培养液中将 进行免疫化学检测，以及它们在细胞内的表达 将通过信使RNA的转录来确定。 假设的机制和条件 抑制炎性细胞因子的产生将会发生 调查过了。进一步推测，抗PG的IgA抗体 脂多糖和其他抗原下调抗原提呈细胞 牙龈单核巨噬细胞和B细胞的活性 淋巴细胞，它负责免疫的永久化 对牙周病原体的反应。据推测，这种情况 调节失调的反应导致慢性前列腺炎的持续 破坏性炎症，而不是消除病原体。这个 免疫球蛋白A介导的抗原提呈能力的调节 牙龈单核巨噬细胞、血单核细胞和B细胞 淋巴细胞将根据以下方面进行评估： 重要的“第二信号”表面分子(B7.1、B7.2和Cd$) Th3细胞与初诊T淋巴细胞的相互作用 和二次免疫反应。T细胞的反应能力 在IgA的影响下对这些细胞递呈的PG抗原的作用 抗体也将被检测出来。如果发现IgA抗体 对炎症反应有改善作用， 免疫反应的永久化，然后采取措施加强 血清对牙周病原体的IgA抗体反应可能 构成了一种新的治疗方法。

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.