2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38821MMP functional activity is regulated by four mechanisms: by positive and negative transcriptional controls of MMP genes, by activation from latent state, by differences in substrate specificity, and modulation by serum inhibitors or tissue inhibitors of metallopropeinases (TIMPs). MMPs even have more strong correlation to periodontal diseases, since MMPs are the major players in collagen breakdown during periodontal tissue destruction . Some studies in the past years had indicated the association between selected candidate gene polymorphisms (Fcγreceptor,IL-1,IL-2,IL-6, IL-10, MMPs/TIMPs, TNF-α ect.) and the susceptibility to periodontitis. TGF-β1 has therapeutic and pathologic potential. Periodontopathogens could induce the releasr of TGF-β1 from mononuclear phagocytes. TGF-β1 was expressed during the early and late stage of periodontal disease. The promoter polymorphism (-509 C/T) of TGF-β1 is associated with the susceptibility to chronic periodontitis in the Brazilian Cacasians, but not in Czech Caucasians. It is clear that periodontal cells actively participate in the innate immuneresponse against dental plaque bacteria. Theses cells express different types of TLRs. Periodontitis is a unique phenomena of one of the host-microbe interactions. The TLR signaling results in innate immune responses involving the release of antibacterial peptides and neutrophil recruiting chemokine (IL-8). TLR signaling serves to limit pathogenic infections and to prevent commensal organisms from breaching the epithelial barrier. In the epithelium and connective tissue via TLR signaling, the stimulated cells could produce an array of cytokines, chemokines, and other mediators that promote inflammation and immune cell infiltration. Additional cytokines produced by infiltrated memory T cells would amplify the inflammatory reaction, leading to destruction of connective tissue and bone. Periodontitis is highly complex and multi-factorial. Investigation into TLR SNPs in periodontitis individuals should provide some insight into the role of the immune system in maintaining periodontal health and combating periodontal disease. During the past few years, several genes have been individually sequenced for association with periodontitis. Different studies have been conducted in varied populations and ethnicities. Frequencies of the genetic marker of interest may show large heterogenecity between races Variation in genotype frequencies across diverse population may affect the number of individuals at increased risk for a disease, and population substructure imbalances may create serious differences in genotype frequencies of the compared groups in gene-disease association studies Susceptible genes polymorphisms including MMPs(MMP-1、-2、-3、-8、 -9 及-12)，TIMPs (TIMP-1、-2、-3)、interleukin(IL-2、-8、-16、-17)、TGF-β、 antigen-recognition-related receptors(CD14、TLR-2、TLR-4) shall be analysed by polymerase chain-restriction fragment length polymorphism analysis.We shall also investigate whether the nucleotide transition will effect the protein expression of the cytokines/mediators which shall be analyzed with ELISA in the samples of GCF, saliva and the supernatants of whole-blood cell cultures. Our data shall provide functional evidence in the association between selected gene plomoyphisms , protein activity and the susceptibility to periodontitisMMPs 的功能性表現是受四個機轉(mechanisms)的調控: MMPs 的陰(negative)/陽 (positive) 轉錄(transcription) 、潛在狀況(latent state) 的活化(activation) 、substrate specificity、血清性inhibitors 及組織性inhibitors(TIMPs)的modulation。 MMPs 與牙周 組織的破壞有強烈的相關性，因為MMPs 是牙周組織的破壞時，膠原蛋白纖維(collagen) 破壞的重要介質。許多有關MMPs 及TIMPs 的基因多型性的研究探討它們與人類各種 疾病(包括牙周炎)的感受性及/或嚴重性。 有些過去的研究指出牙周炎的感受性(susceptibility) 與 Fc-gamma receptor 、 Interleukin(IL)-1 、IL-6 、IL-10 及metalloproteinase-1 、TNF-α 等基因多型性(gene polymorphisms)有關。TGF-β1 是一種cytokine，於組織受傷及炎性細胞受細菌或其產物 的影響時會釋放出來，但TGF-β1 具有治療(therapeutic)與致病(pathologic)的潛能 (potential) 。牙周病原菌能引起mononuclear phagocytes (in vitro)釋放出TGF-β1，也可於 牙周病的早期與晚期偵測到。 TGF-β1 之promoter polymorphism (-509 C/T)與Brazilian Caucasians 之慢性牙周炎有關，但與Czech Caucasians 之慢性牙周炎則無關。 牙周細胞積極參與innate immune response 以對抗牙菌斑細菌，牙周細胞會表現各種 的toll-like receptors(TLRs) 。 牙周炎是很典型的宿主- 微生物間的互相反應 (interactions)。TLRs 的訊息傳遞(signal)結果使innate immune response 釋出anti-bacterial peptide 及募集neutrophils 的IL-8 ，因此TLRs 的表現可謂是對細菌的侵犯(invasion)時， 激發(trigger)炎性反應的工具，顯示TLRs 於牙周炎扮演某一角色。 TLRs 的基因多型性 與牙周炎的感受性在一些族群亦有被探討。 雖然某些基因在宿主的免疫反應方面扮有某些角色，但是，這些結果乃具有爭議性 且顯示族群間的極大差異。本計畫將對感受性基因，包括MMPs(MMP-1、-2、-3、-8、 -9 及-12) ，TIMPs (TIMP-1、-2 、-3) 、interleukin(IL)-2 、-8 、-16 、-17) 、TGF-β 、 antigen-recognition-related receptors(CD14 、TLR-2 、TLR-4) 將以polymerase chain-restriction fragment length polymorphism analysis 來探討。本計畫亦設計來探討基因 的nucleotide transition 結果，在宿主的細胞激素(cytokines)等炎性介質(mediators)的表現 (protein or mRNA)是否有影響。這可藉由分析牙周炎患者唾液的、血漿的、全血細胞培 養液的細胞激素(介質)濃度偵測得知。而偵測的方法可包括利用ELISA。在過去已有許 關於多種細胞激素(介質)於牙周炎病人的唾液中或牙齦溝中促炎性介質的表現，及多數 的基因研究也有注意到對免疫調整或新陳代謝(immunoregulation or metabolism)有關的 細胞激素(介質)對於牙周炎感受性的角色，但有關於功能上的表現(functional implication) 的關係的研究報告則尚甚缺乏。基因的結構上缺陷(structure gene defect)會影響基因多型 性在炎性介質的量上(quantitative )的反應程度，在基因多型性的調整機轉有可能改變這 種量上的改變。本計畫即亦是要在基因多型性、基因功能性與牙周炎的關係間提供功能 上的證據(functional evidence)。Project