Yamamoto M, Kawabata K, Fujihashi K, McGhee J R, Van Dyke T E, Bamberg T V, Hiroi T, Kiyono H
Department of Oral Biology, University of Alabama at Birmingham Medical Center 35294-2170, USA.
Am J Pathol. 1996 Jan;148(1):331-9.
Inflamed gingival tissues are enriched in macrophages (MOs) and CD4-positive T cells; however, T helper-type cytokines such as interleukin (IL)-2 and IL-4 are absent. Therefore, we investigated whether a relationship exists between IL-4 receptor (IL-4R) expression and MO persistence in the absence of exogenous IL-4. Gingival MOs, when compared with monocyte(MN)/MOs from peripheral blood mononuclear cells, expressed high levels of IL-4R mRNA. Furthermore, in vitro cultures of gingival MOs remained viable whereas identically treated peripheral blood MN/MOs rapidly lost viability. However, when gingival MOs were incubated with recombinant IL-4 (rIL-4), the cell viability was dramatically reduced. When the frequency of apoptotic cells was assessed in rIL-4-treated gingival MO cultures, higher numbers of apoptotic cells were noted in rIL-4-treated versus control cultures. Furthermore, rIL-4-treated MOs from inflamed gingiva showed DNA fragmentation as assessed by electrophoresis. These findings clearly show that addition of exogenous rIL-4 to gingival MO cultures leads to cell death by apoptosis. This finding would suggest that topical application of rIL-4 may inhibit the persistence of MOs in adult periodontitis, which could then lead to decreased inflammation.
炎症牙龈组织中富含巨噬细胞（MOs）和CD4阳性T细胞；然而，诸如白细胞介素（IL）-2和IL-4等辅助性T细胞细胞因子却不存在。因此，我们研究了在无外源性IL-4的情况下，IL-4受体（IL-4R）表达与MOs持续性之间是否存在关联。与来自外周血单个核细胞的单核细胞（MN）/MOs相比，牙龈MOs表达高水平的IL-4R mRNA。此外，牙龈MOs的体外培养物仍保持活力，而经过相同处理的外周血MN/MOs则迅速丧失活力。然而，当牙龈MOs与重组IL-4（rIL-4）一起孵育时，细胞活力显著降低。当在rIL-4处理的牙龈MO培养物中评估凋亡细胞的频率时，发现rIL-4处理组的凋亡细胞数量高于对照组。此外，通过电泳评估，来自炎症牙龈的rIL-4处理的MOs显示出DNA片段化。这些发现清楚地表明，向牙龈MO培养物中添加外源性rIL-4会导致细胞通过凋亡死亡。这一发现表明，局部应用rIL-4可能会抑制MOs在成人牙周炎中的持续性，进而导致炎症减轻。
