Alikhani M, Alikhani Z, Graves D T
Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, MA 02118, USA.
J Dent Res. 2004 Sep;83(9):671-6. doi: 10.1177/154405910408300903.
During periods of periodontal attachment loss, one of the most significant cellular changes is a decrease in the number of fibroblasts. We previously demonstrated that LPS induces apoptosis of fibroblastic cells in vivo, largely through TNF-alpha. We conducted in vivo experiments by subcutaneous inoculation of LPS in wild-type, TNFR1-/-R2-/-, TNFR1-/-, and TNFR2-/- mice to identify which TNF receptors are involved and the specific caspase pathway activated. LPS stimulated apoptosis through TNFR1 but not TNFR2, which was accompanied by the induced expression of 12 apoptotic genes. Fluorometric studies demonstrated that LPS in vivo significantly increased caspase-8 and caspase-3 activity, which was also dependent on TNF receptor signaling. By the use of specific caspase inhibitors, caspases-3 and -8 were shown to play an important role in LPS-induced apoptosis in vivo. Thus, LPS acts through TNFR1 to modulate the expression of apoptotic genes and activate caspases-3 and -8.
在牙周附着丧失期间，最显著的细胞变化之一是成纤维细胞数量减少。我们之前证明，脂多糖（LPS）在很大程度上通过肿瘤坏死因子-α（TNF-α）诱导成纤维细胞在体内发生凋亡。我们通过在野生型、TNFR1-/-R2-/-、TNFR1-/-和TNFR2-/-小鼠皮下接种LPS进行体内实验，以确定哪些肿瘤坏死因子受体参与其中以及激活的特定半胱天冬酶途径。LPS通过TNFR1而非TNFR2刺激凋亡，这伴随着12个凋亡基因的诱导表达。荧光测定研究表明，体内的LPS显著增加了半胱天冬酶-8和半胱天冬酶-3的活性，这也依赖于肿瘤坏死因子受体信号传导。通过使用特异性半胱天冬酶抑制剂，发现半胱天冬酶-3和-8在LPS诱导的体内凋亡中起重要作用。因此，LPS通过TNFR1发挥作用，调节凋亡基因的表达并激活半胱天冬酶-3和-8。
