Gu Ying, Lee Hsi-Ming, Sorsa Timo, Simon Sanford R, Golub Lorne M
Department of General Dentistry, Stony Brook University, Stony Brook, NY, USA.
FEMS Immunol Med Microbiol. 2010 Mar;58(2):218-25. doi: 10.1111/j.1574-695X.2009.00625.x. Epub 2009 Nov 10.
Chronic periodontitis is the most common chronic inflammatory disease and has been associated with an increased risk for serious medical conditions including cardiovascular disease (CVD). Endotoxin (lipopolysaccharide), derived from periodontopathogens, can induce the local accumulation of mononuclear cells in the inflammatory lesion, increasing proinflammatory cytokines and matrix metalloproteinases (MMPs), resulting in the destruction of periodontal connective tissues including bone. In this study, we show that doxycycline, originally developed as a broad-spectrum tetracycline antibiotic (and, more recently, as a nonantimicrobial therapy for chronic inflammatory periodontal and skin diseases), can inhibit extracellular matrix degradation in cell culture mediated by human peripheral blood-derived monocytes/macrophages. The mechanisms include downregulation of cytokines and MMP-9 protein levels and the inhibition of the activities of both collagenase and MMP-9. These pleiotropic, but nonantibiotic, effects of doxycycline explain, at least in part, its therapeutic potential for various chronic inflammatory diseases including periodontitis, and may reduce the risks of systemic diseases (e.g. CVDs, less manageable diabetes) associated with this and other local diseases.
慢性牙周炎是最常见的慢性炎症性疾病，并且与包括心血管疾病（CVD）在内的严重医疗状况风险增加有关。源自牙周病原体的内毒素（脂多糖）可诱导炎症病变中单核细胞的局部积聚，增加促炎细胞因子和基质金属蛋白酶（MMPs），导致包括骨骼在内的牙周结缔组织破坏。在本研究中，我们表明强力霉素最初作为一种广谱四环素抗生素开发（最近，作为一种用于慢性炎症性牙周和皮肤疾病的非抗菌疗法），可以抑制人外周血来源的单核细胞/巨噬细胞介导的细胞培养中的细胞外基质降解。其机制包括细胞因子和MMP-9蛋白水平的下调以及胶原酶和MMP-9活性的抑制。强力霉素的这些多效性但非抗生素作用至少部分解释了其对包括牙周炎在内的各种慢性炎症性疾病的治疗潜力，并可能降低与此及其他局部疾病相关的全身性疾病（如心血管疾病、较难控制的糖尿病）的风险。
