Taniguchi Yoshifumi, Kohno Keizo, Inoue Shin-ichiro, Koya-Miyata Satomi, Okamoto Iwao, Arai Norie, Iwaki Kanso, Ikeda Masao, Kurimoto Masashi
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc, Fujisaki 675-1, Okayama 702-8006, Japan.
Int Immunopharmacol. 2003 Sep;3(9):1313-24. doi: 10.1016/s1567-5769(03)00132-2.
We have shown previously that in addition to IL-4, IL-5 and IL-10, antigen-specific interferon-gamma (IFN-gamma) production by spleen cells from ovalbumin (OVA)/Alum-immunized mice is inhibited by the administration of royal jelly (RJ). Since it has been shown that both Th1 and Th2 cytokines play pathogenic roles in the generation of atopic dermatitis (AD), we have examined whether RJ suppresses the development of AD-like skin lesions in NC/Nga mice induced by repeated application of picryl chloride (PiCl) under specific pathogen-free (SPF) conditions. Oral administration of RJ to the PiCl-treated NC/Nga mice inhibited the development of AD-like skin lesions in these mice as exemplified by the significant decrease in the total skin severity scores and the decrease in hypertrophy, hyperkeratosis, and infiltration of the epidermis and corium by inflammatory cells. IFN-gamma production by spleen cells from PiCl-treated NC/Nga mice in response to TNP-KLH was partially but significantly inhibited by the oral administration of RJ, while IFN-gamma production by Con A-stimulated spleen cells was not affected. Since inducible nitric oxide (NO) synthase (iNOS)-derived NO has been suggested as an important immunoregulatory mediator in inflammatory autoimmune diseases, we have also examined the expression of iNOS in the dorsal skin lesions of PiCl-treated NC/Nga mice. Interestingly, the expression of iNOS was significantly increased in the skin lesions of RJ-administered mice compared with those of control PBS-administered mice. Thus, our results suggest that RJ suppresses the development of AD-like skin lesions in PiCl-treated NC/Nga mice, possibly by a combination of down-regulating TNP-specific IFN-gamma production and up-regulating iNOS expression.
我们之前已经表明，除白细胞介素-4、白细胞介素-5和白细胞介素-10外，经卵清蛋白（OVA）/明矾免疫的小鼠脾脏细胞产生的抗原特异性干扰素-γ（IFN-γ）会受到蜂王浆（RJ）给药的抑制。由于已经表明Th1和Th2细胞因子在特应性皮炎（AD）的发生中都起致病作用，我们研究了RJ是否能抑制在无特定病原体（SPF）条件下反复涂抹苦味酸（PiCl）诱导的NC/Nga小鼠中类AD皮肤病变的发展。对经PiCl处理的NC/Nga小鼠口服RJ可抑制这些小鼠中类AD皮肤病变的发展，这表现为总皮肤严重程度评分显著降低，以及炎症细胞引起的表皮和真皮肥厚、角化过度及浸润减少。经PiCl处理的NC/Nga小鼠脾脏细胞对三硝基苯-钥孔戚血蓝蛋白（TNP-KLH）反应产生的IFN-γ，经口服RJ后受到部分但显著的抑制，而经刀豆蛋白A（Con A）刺激的脾脏细胞产生的IFN-γ不受影响。由于诱导型一氧化氮（NO）合酶（iNOS）衍生的NO已被认为是炎症性自身免疫疾病中的一种重要免疫调节介质，我们还研究了经PiCl处理的NC/Nga小鼠背部皮肤病变中iNOS的表达。有趣的是，与给予对照磷酸盐缓冲盐水（PBS）的小鼠相比，给予RJ的小鼠皮肤病变中iNOS的表达显著增加。因此，我们的结果表明，RJ可能通过下调TNP特异性IFN-γ产生和上调iNOS表达的组合来抑制经PiCl处理的NC/Nga小鼠中类AD皮肤病变的发展。
