Suzuki Shintaro, Kokubu Fumio, Kawaguchi Mio, Homma Tetsuya, Odaka Miho, Watanabe Shin, Ieki Koshi, Matsukura Satoshi, Kurokawa Masatsugu, Takeuchi Hiroko, Sasaki Yoshiko, Huang Shau-Ku, Adachi Mitsuru, Ota Hidekazu
First Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
Int Arch Allergy Immunol. 2007;143 Suppl 1:89-94. doi: 10.1159/000101413. Epub 2007 May 1.
Interleukin (IL)-17F is a recently discovered cytokine and is derived from a panel of limited cell types, such as activated CD4+ T cells, basophils, and mast cells. IL-17F is known to induce several cytokines and chemokines. However, its involvement in airway inflammation has not been well understood. To this end, the expression of IL-17F and the inhibitory effects of glucocorticoids on its expression in a mouse model of asthma were examined.
Five-week-old BALB/c male mice were sensitized by intraperitoneal injection (i.p.) of ovalbumin (OVA) with alum, and challenged by daily inhalation of aerosolized 1% OVA. 24 h after last challenge (OVA/OVA), the expression of IL-17F was examined in lung tissues by immunohistochemistry and reverse-transcription polymerase chain reaction. Control mice were sensitized and challenged with saline (Sham/Sham). In addition, a group OF OVA-sensitized mice received i.p. injection of water-soluble dexamethasone (DEX) in saline 1 h before ova challenge (OVA/DEX).
In sham-challenged mice, IL-17F was not expressed in the lungs, while, in contrast, IL-17F was predominantly expressed in bronchial epithelial cells in addition to the infiltrating inflammatory cells in OVA/OVA mice. Further, the expression of IL-17 F was significantly attenuated by the treatment of mice with DEX.
These results suggest that bronchial epithelium-derived IL-17F may represent a new pharmacological target for glucocorticoids and may play a role in allergic asthma.
白细胞介素(IL)-17F是一种最近发现的细胞因子,由有限的几种细胞类型产生,如活化的CD4 + T细胞、嗜碱性粒细胞和肥大细胞。已知IL-17F可诱导多种细胞因子和趋化因子。然而,其在气道炎症中的作用尚未得到充分了解。为此,我们检测了哮喘小鼠模型中IL-17F的表达以及糖皮质激素对其表达的抑制作用。
5周龄的BALB/c雄性小鼠通过腹腔注射(i.p.)卵清蛋白(OVA)和明矾进行致敏,然后每天吸入雾化的1%OVA进行激发。在最后一次激发(OVA/OVA)后24小时,通过免疫组织化学和逆转录聚合酶链反应检测肺组织中IL-17F的表达。对照小鼠用生理盐水进行致敏和激发(假手术/假手术)。此外,一组OVA致敏小鼠在OVA激发前1小时腹腔注射溶于生理盐水的水溶性地塞米松(DEX)(OVA/DEX)。
在假手术激发的小鼠中,肺组织中未检测到IL-17F的表达,而相比之下,在OVA/OVA小鼠中,除浸润的炎性细胞外,IL-17F主要表达于支气管上皮细胞中。此外,DEX处理可显著减弱小鼠中IL-17F的表达。
这些结果表明,支气管上皮来源的IL-17F可能是糖皮质激素的一个新的药理学靶点,并可能在过敏性哮喘中发挥作用。