Sakai Shinobu, Akiyama Hiroshi, Sato Yuji, Yoshioka Yasuo, Linhardt Robert J, Goda Yukihiro, Maitani Tamio, Toida Toshihiko
Graduate School of Pharmaceutical Sciences, Chiba University, Inage-ku, Chiba 263-8522, Japan.
J Biol Chem. 2006 Jul 21;281(29):19872-80. doi: 10.1074/jbc.M509058200. Epub 2006 Apr 19.
Chondroitin sulfate (CS) was administered orally to BALB/c mice immunized intraperitoneally with ovalbumin (OVA) and/or dinitrophenylated OVA. The titers of antigen-specific IgE and IgG1 in mouse sera were determined. The antigen-specific IgE production by mice fed ad libitum with CS was significantly inhibited. We also examined the effect of feeding CS on immediate-type hypersensitivity. One hour after antigen stimulation, the ears of mice fed with CS swelled less than those of the control mice. Furthermore, the rise in serum histamine in the mice fed with CS under active systemic anaphylaxis was significantly lower than that in the controls. We next examined the pattern of cytokine production by splenocytes from mice followed by re-stimulation with OVA in vitro. The splenocytes from the mice fed with CS produced less interleukin (IL)-5, IL-10, and IL-13 than those from the control group. In contrast, the production of interferon-gamma and IL-2 by the splenocytes of mice fed with CS was not significantly different from those in the control mice. In addition, the production of transforming growth factor-beta from the splenocytes of mice fed with CS was significantly higher than that of the control mice. Furthermore, we showed that the percentages of CD4(+) cells, CD8(+) cells, and CD4(+)CD25(+) cells in the splenocytes of mice fed with CS are significantly higher than those of the control. These findings suggest that oral intake of CS inhibits the specific IgE production and antigen-induced anaphylactic response by up-regulating regulatory T-cell differentiation, followed by down-regulating the Th2 response.
将硫酸软骨素（CS）口服给予经腹腔注射卵清蛋白（OVA）和/或二硝基苯基化OVA免疫的BALB/c小鼠。测定小鼠血清中抗原特异性IgE和IgG1的滴度。随意喂食CS的小鼠的抗原特异性IgE产生受到显著抑制。我们还研究了喂食CS对速发型超敏反应的影响。抗原刺激1小时后，喂食CS的小鼠耳朵肿胀程度小于对照小鼠。此外，在主动全身过敏反应中，喂食CS的小鼠血清组胺升高明显低于对照组。接下来，我们检测了用OVA体外再次刺激后小鼠脾细胞产生细胞因子的模式。喂食CS的小鼠的脾细胞产生的白细胞介素（IL）-5、IL-10和IL-13比对照组少。相比之下，喂食CS的小鼠脾细胞产生的干扰素-γ和IL-2与对照小鼠没有显著差异。此外，喂食CS的小鼠脾细胞产生的转化生长因子-β明显高于对照小鼠。此外，我们发现喂食CS的小鼠脾细胞中CD4(+)细胞、CD8(+)细胞和CD4(+)CD25(+)细胞的百分比明显高于对照组。这些发现表明，口服CS通过上调调节性T细胞分化，随后下调Th2反应，抑制特异性IgE产生和抗原诱导的过敏反应。
