Akimoto R, Pawankar R, Yagi T, Baba S
Department of Otolaryngology, Nippon Medical School, Sendagi, Tokyo, Japan.
ORL J Otorhinolaryngol Relat Spec. 2000 Sep-Oct;62(5):257-65. doi: 10.1159/000027756.
The molecular and cellular factors resulting in the pathologic features of acquired and congenital cholesteatomas are not completely known. Recently, proinflammatory cytokines like interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) have been shown to induce bone resorption, in vitro. To elucidate the key molecules involved in bone resorption and cell infiltration associated with cholesteatoma, we examined the in vivo levels of IL-1 alpha and TNF-alpha, intercellular adhesion molecule-1 (ICAM-1) and lymphocyte functional antigen-1 (LFA-1) in acquired and congenital cholesteatomas, by reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ELISA. Increased levels of IL-1 and TNF-alpha were detected in both types of cholesteatomas as compared to normal skin. Increased ICAM-1 expression and LFA-1+ cells were detected in acquired but not congenital cholesteatoma. Strong correlation was detected between TNF-alpha and bone resorption in both types of cholesteatoma, and between TNF-alpha and ICAM, TNF-alpha and severity of infection, or cell infiltration in acquired cholesteatoma. No correlation existed between various parameters and IL-1 alpha. These results suggest that TNF-alpha may play a crucial role in the pathogenesis of both acquired and congenital cholesteatomas by regulating bone resorption and cell infiltration.
导致获得性和先天性胆脂瘤病理特征的分子和细胞因素尚不完全清楚。最近,白细胞介素-1α(IL-1α)和肿瘤坏死因子-α(TNF-α)等促炎细胞因子已被证明在体外可诱导骨吸收。为了阐明与胆脂瘤相关的骨吸收和细胞浸润所涉及的关键分子,我们通过逆转录聚合酶链反应、免疫组织化学和酶联免疫吸附测定法检测了获得性和先天性胆脂瘤中IL-1α、TNF-α、细胞间黏附分子-1(ICAM-1)和淋巴细胞功能抗原-1(LFA-1)的体内水平。与正常皮肤相比,在两种类型的胆脂瘤中均检测到IL-1和TNF-α水平升高。在获得性胆脂瘤中检测到ICAM-1表达增加和LFA-1+细胞,但在先天性胆脂瘤中未检测到。在两种类型的胆脂瘤中均检测到TNF-α与骨吸收之间、以及在获得性胆脂瘤中TNF-α与ICAM、TNF-α与感染严重程度或细胞浸润之间存在强相关性。各种参数与IL-1α之间不存在相关性。这些结果表明,TNF-α可能通过调节骨吸收和细胞浸润在获得性和先天性胆脂瘤的发病机制中起关键作用。