Elucidation of receptors for salivary protein histatin in human gingival fibroblast

牙周病导致口腔细菌接触牙齿和口腔组织。结果显示牙槽骨被破坏。这些都是由炎性宿主细胞之间复杂的相互作用产生的。我们报道了人牙周成纤维细胞(HGF)在脂多糖或牙周细菌来源的蛋白酶的刺激下，对组织的破坏和炎性细胞因子的产生。组抑素的作用是杀灭念珠菌的活性和抑制龋病的细菌增殖。研究还发现，艾滋病患者体内组抑素的表达减少。我们阐明了组他汀类药物对牙周细菌蛋白酶的失活和对HGF增殖的促进作用。当研究组抑素在口腔组织中的定位时，我们可以预料到它们的功能。用抗组蛋白抗体对口腔组织进行染色，发现腮腺组织中存在组抑素…多为颌下腺、舌颗粒层和颊粘膜棘细胞层。组蛋白在腮腺和颌下腺中特异表达。组蛋白5是组蛋白家族的成员，与白念珠菌热休克蛋白(HSP)SSA 1/2p结合。结果表明，该制剂具有抑菌作用。然后，我们研究了组蛋白是否与人热休克蛋白相互作用。HSC70是热休克蛋白家族中的一员，它与组蛋白结合，结合在HSC70的多肽结合区。组素通过内吞作用转运到细胞内，组素/HSC70复合体转运到细胞核中。由于这在细胞的热处理中是显著的，所以有人认为组蛋白的移位依赖于HSC70。热休克蛋白的功能是蛋白质的结构形成、变性蛋白质的复性和防止凝聚蛋白质。HSC70与DNA复制和转录有关，是Toll样受体的配体。提示HGF的增殖和存活与组蛋白有关。组抑素与细胞因子之间的相互作用尚未见报道。此外，对组蛋白和热休克蛋白之间的生理功能的详细研究似乎与组蛋白的药物设计发现有关。这可能适用于口腔疾病，并应用于生殖领域。较少

Periodontal diseases cause oral bacteria that contact with teeth and oral tissues. The results indicate the destruction of alveolar bones. These are generated by the complicated interaction between inflammatory host cells. We reported that the tissue destruction and production of inflammatory cytokines from human gingival fibroblast (HGF) were stimulated by LPS or protease derived from periodontal bacteria. Functions of histatins are a Candidacidal activity and a suppression of bacterial proliferation for caries. And it found the reduced expression of histatins for AIDS. We clarified about inactivation of proteases from periodontal bacteria and enhancement of proliferation in HGF by histatins. When the localization of histatins in a mouth organization was investigated, we may be expected the functions of those. And the identification of molecles that interact with histatins was investigated.When oral tissues were stained with anti-histatin antibody, histatins were existed in a parotid, … More a submandibular gland, tongue stratum granulosum and buccal mucosa prickle-cell layer. Histatins were specifically expressed in the parotid and the submandibular gland. And histatins may be transported into intercellular or intracellular space of tissues and cells.Histatin 5, a member of histatin family, bound to heat shock protein (HSP) SSA 1/2p from Candida albicans. The result showed antimicrobial action. Then, we investigated whether histatin was interacted with human HSPs. HSC70 that is a member of HSPs was associated with histatin, which bound to the peptide-binding domain of HSC70. Histatin was transported into the cells by the endocytosis and histatin/HSC70 complex was translocated into nuclei. Since this was remarkable at heat treatment of cells, it was suggested that the translocation of histatin is dependent on HSC70. The functions of HSPs are structural formation of proteins, refolding of denatured proteins and prevention of condensational proteins. And HSC70, in relation to a DNA replication and transcription, serves as a ligand of Toll-like receptor. These results suggested that the proliferation and survival of HGF was related with histatin. The interaction between histatins and cellular factors has not yet been reported. Moreover, it seems that detailed study for the physiological functions between histatin and HSP is connected with drug design discovery for histatin. And this could apply to the oral diseases and employ a field of reproduction. Less