Palmqvist P, Lundberg P, Lundgren I, Hänström L, Lerner U H
Department of Oral Cell Biology, Umeå University, Umeå, Sweden.
J Dent Res. 2008 Jun;87(6):558-63. doi: 10.1177/154405910808700614.
Interleukin-6 (IL-6)-type cytokines are pleiotropic molecules capable of stimulating bone resorption and expressed by numerous cell types. In the present study, we tested the hypothesis that gingival fibroblasts may exert local osteotropic effects through production of IL-6 and related cytokines. IL-6-type cytokine expression and regulation by IL-1beta and tumor necrosis factor-alpha (TNF-alpha) were studied in fibroblasts from the non-inflamed gingiva of healthy individuals. Constitutive mRNA expression of IL-6, IL-11, and leukemia inhibitory factor (LIF), but not of oncostatin M (OSM), was demonstrated, as was concentration-dependent stimulation of IL-6 and LIF mRNA and of protein by IL-1beta and TNF-alpha. IL-11 mRNA and protein were concentration-dependently stimulated by IL-1beta. The signaling pathway involved in IL-6 and LIF mRNA stimulation involved MAP kinases, but not NF-kappaB. The findings support the view that resident cells may influence the pathogenesis of periodontal disease through osteotropic IL-6-type cytokine production mediated by activation of MAP kinases.
IL-1alpha (interleukin-1alpha); IL-1beta (interleukin-1beta); IL-6 (interleukin-6); IL-11 (interleukin-11); LIF (leukemia inhibitory factor); OSM (oncostatin M); alpha(1)-coll. I (alpha(1)-collagen I); ALP (alkaline phosphatase); BMP-2 (bone morphogenetic protein-2); OC (osteocalcin); BSP (bone sialoprotein); TNFR I (tumor necrosis factor receptor I); TNFR II (tumor necrosis factor receptor II); IL-1R1 (interleukin-1 receptor 1); GAPDH (glyceraldehyde-3-phosphate dehydrogenase); RPL13A (ribosomal protein L13A); mRNA (messenger ribonucleic acid); cDNA (complementary deoxyribonucleic acid); PCR (polymerase chain-reaction); BCA (bicinchoninic acid); ELISA (enzyme-linked immunosorbent assay); alpha-MEM (alpha modification of Minimum Essential Medium); and FCS (fetal calf serum).
白细胞介素-6（IL-6）型细胞因子是多效性分子，能够刺激骨吸收，由多种细胞类型表达。在本研究中，我们检验了如下假设：牙龈成纤维细胞可能通过产生IL-6及相关细胞因子发挥局部促骨作用。我们研究了健康个体非炎症牙龈成纤维细胞中IL-6型细胞因子的表达以及IL-1β和肿瘤坏死因子-α（TNF-α）对其的调节作用。结果显示存在IL-6、IL-11和白血病抑制因子（LIF）的组成型mRNA表达，但抑瘤素M（OSM）没有，同时IL-1β和TNF-α对IL-6和LIF的mRNA及蛋白呈浓度依赖性刺激。IL-1β对IL-11的mRNA和蛋白呈浓度依赖性刺激。刺激IL-6和LIF mRNA的信号通路涉及丝裂原活化蛋白激酶（MAP激酶），但不涉及核因子-κB（NF-κB）。这些发现支持以下观点：驻留细胞可能通过由MAP激酶激活介导的促骨IL-6型细胞因子产生影响牙周病的发病机制。
IL-1α（白细胞介素-1α）；IL-1β（白细胞介素-1β）；IL-6（白细胞介素-6）；IL-11（白细胞介素-11）；LIF（白血病抑制因子）；OSM（抑瘤素M）；α(1)-胶原I（α(1)-胶原蛋白I）；碱性磷酸酶（ALP）；骨形态发生蛋白-2（BMP-2）；骨钙素（OC）；骨唾液蛋白（BSP）；肿瘤坏死因子受体I（TNFR I）；肿瘤坏死因子受体II（TNFR II）；白细胞介素-1受体1（IL-1R1）；甘油醛-3-磷酸脱氢酶（GAPDH）；核糖体蛋白L13A（RPL13A）；信使核糖核酸（mRNA）；互补脱氧核糖核酸（cDNA）；聚合酶链反应（PCR）；二辛可宁酸（BCA）；酶联免疫吸附测定（ELISA）；α-最低必需培养基（α-MEM）；胎牛血清（FCS）。
