Oral GABA treatment downregulates inflammatory responses in a mouse model of rheumatoid arthritis.
Oral GABA treatment downregulates inflammatory responses in a mouse model of rheumatoid arthritis.
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口服GABA治疗下调类风湿关节炎小鼠模型中的炎症反应。
DOI：
10.3109/08916934.2011.571223
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发表时间：
2011-09
期刊：
影响因子：
3.5
通讯作者：
Kaufman DL
中科院分区：
文献类型：
--
作者：
Tian J;Yong J;Dang H;Kaufman DL
目前治疗类风湿性关节炎（RA）有长期的副作用，因此需要新的治疗方法，可以安全地帮助控制疾病。越来越多的人认识到，免疫细胞上的GABA受体（GABA-R）提供了可用于调节免疫细胞活性的新靶点。在这里，我们首次表明，激活外周GABA-Rs可以抑制疾病的发展，在胶原诱导的关节炎（CIA）小鼠模型的RA。接受口服GABA的小鼠CIA的发病率降低，而那些确实发生CIA的小鼠症状较轻。GABA处理小鼠的T细胞对胶原蛋白的增殖反应降低，其APC促进胶原蛋白反应性T细胞增殖的能力降低。因此，GABA下调T细胞自身免疫和APC活性。来自GABA处理的小鼠的胶原反应性T细胞在GABA离体存在下显示出降低的回忆反应，表明GABA消耗并没有使这些细胞对GABA脱敏。GABA处理的小鼠具有减少的胶原反应性IgG 2a，但不是IgG 1抗体，与减少的Th 1帮助一致。血清抗胶原IgG 2a抗体水平与CIA疾病评分显著相关。我们的研究结果表明，外周GABA受体的激活可能提供了一种新的方式来调节T细胞，B细胞和APC的活性，并有助于改善RA和其他炎症性疾病。
Current treatments for rheumatoid arthritis (RA) have long-term side effects such that new treatments are needed that can safely help manage the disease. There is a growing appreciation that GABA receptors (GABA-Rs) on immune cells provide new targets that can be used to modulate immune cell activity. Here, we show for the first time that activation of peripheral GABA-Rs can inhibit the development of disease in the collagen-induced arthritis (CIA) mouse model of RA. Mice that received oral GABA had a reduced incidence of CIA, and those mice that did develop CIA had milder symptoms. T cells from GABA-treated mice displayed reduced proliferative responses to collagen and their APC had a reduced ability to promote the proliferation of collagen-reactive T cells. Thus, GABA downregulated both T-cell autoimmunity and APC activity. Collagen-reactive T cells from GABA-treated mice displayed reduced recall responses in the presence of GABA ex vivo, indicating that GABA consumption did not desensitize these cells to GABA. GABA-treated mice had reduced collagen-reactive IgG2a, but not IgG1 antibodies, consistent with reduced Th1 help. The levels of serum anti-collagen IgG2a antibodies were correlated significantly with the CIA disease scores of individual mice. Our results suggest that activation of peripheral GABA-Rs may provide a new modality to modulate T cell, B cell, and APC activity and help ameliorate RA and other inflammatory diseases.
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影响因子：
82.9
作者：
Tian, JD;ClareSalzler, M;Kaufman, DL
通讯作者：
Kaufman, DL
影响因子：
3.3
作者：
Reyes-Garcia, Maria Guadalupe;Hernandez-Hernandez, Francisca;Garcia-Tamayo, Fernando
通讯作者：
Garcia-Tamayo, Fernando
胶原诱导的小鼠关节炎的血清转移。
DOI：
10.1084/jem.158.2.378
发表时间：
1983-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Stuart JM;Dixon FJ
通讯作者：
Dixon FJ
DOI：
10.1073/pnas.0915139107
发表时间：
2010-02-09
影响因子：
11.1
作者：
Bhat, Roopa;Axtell, Robert;Steinman, Lawrence
通讯作者：
Steinman, Lawrence
影响因子：
7.5
作者：
Bergeret, M;Khrestchatisky, M;Chany, C
通讯作者：
Chany, C