Chondroitin sulfate intake inhibits the IgE-mediated allergic response by down-regulating Th2 responses in mice

Chondroitin sulfate intake inhibits the IgE-mediated allergic response by down-regulating Th2 responses in mice
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DOI:
10.1074/jbc.m509058200
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发表时间:
2006-07-21
影响因子:
4.8
通讯作者:
Toida, Toshihiko
Toida, Toshihiko
中科院分区:
生物学2区
文献类型:
--
作者:
Sakai, Shinobu;Akiyama, Hiroshi;Toida, Toshihiko

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用卵清蛋白(OVA)和/或二硝基苯化OVA腹腔免疫BALB/c小鼠,经口给予硫酸软骨素(CS)。测定小鼠血清中抗原特异性IgE和IgG 1的滴度。随意喂食CS的小鼠的抗原特异性IgE产生被显著抑制。我们还研究了喂食CS对速发型超敏反应的影响。抗原刺激后1小时,喂食CS的小鼠的耳朵肿胀程度低于对照小鼠。此外,在主动全身过敏反应下,喂食CS的小鼠血清组胺的升高显著低于对照组。我们接下来检查了在体外用OVA再刺激后小鼠脾细胞产生细胞因子的模式。与对照组相比,饲喂CS的小鼠的脾细胞产生较少的白细胞介素(IL)-5,IL-10和IL-13。与此相反,干扰素-γ和IL-2的生产与CS喂养的小鼠的脾细胞没有显着不同,在对照组小鼠。此外,从饲喂CS的小鼠的脾细胞产生的转化生长因子-β显著高于对照小鼠。此外,我们还发现饲喂CS的小鼠脾细胞中的CD 4(+)细胞、CD 8(+)细胞和CD 4(+)CD 25(+)细胞的百分比显著高于对照组。这些研究结果表明,口服摄入CS抑制特异性IgE的生产和抗原诱导的过敏反应,上调调节性T细胞分化,然后下调Th 2反应。
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.