Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo (UNIFESP), Brazil.
Int Immunopharmacol. 2010 Dec;10(12):1481-5. doi: 10.1016/j.intimp.2010.09.005. Epub 2010 Oct 15.
TLR-4 has also been identified as a receptor for endogenous alarmins, which are increased post transplantation. TLR-4 has also been associated with a polymorphism that could impact graft outcome.
To assess the expression of TLR-4 in kidney transplant patients carrying or not a polymorphism.
TLR-4 polymorphism (A299G/T399I) was studied in 200 renal transplant patients. Healthy volunteers were also enrolled as control group. The polymorphism analysis was performed using restriction enzymes technique (RFLP). Functionality of TLR-4 polymorphism was assessed in samples from controls by quantification of TNF-α after LPS stimulus. TLR-4 and -2 expressions were also analyzed by flow cytometry.
TLR-4 polymorphism was present in 8.5% of renal transplant patients. This polymorphism was associated with impairment in TNF-α secretion. In general, in renal transplant patients, TLR-4 expression in monocytes and in neutrophils was lower than in health volunteers. TLR-2 and TLR-4 expressions in healthy volunteers with A299G/T399I TLR-4 polymorphism was higher than in wild-type genotype healthy volunteers (p<0.01 and p<0.05, respectively), and also higher than A299G/T399I TLR-4 polymorphism renal transplant patients (p<0.05). TLR-2 expression on neutrophils in wild-type genotype renal transplant patients was higher compared to wild-type genotype healthy volunteers, and was also higher in relation to A299G/T399I kidney transplanted patients (p<0.01).
Stable renal transplant patients with TLR-4 polymorphism have a lower expression of TLR-4 and TLR-2 receptors in peripheral mononuclear cells, which ultimately indicate a less responsiveness for alarmins.
TLR-4 也被确定为内源性警报素的受体，这些警报素在移植后会增加。TLR-4 也与一种可能影响移植物结果的多态性有关。
评估携带或不携带多态性的肾移植患者 TLR-4 的表达。
研究了 200 例肾移植患者 TLR-4 多态性（A299G/T399I）。还招募了健康志愿者作为对照组。使用限制性内切酶技术（RFLP）进行多态性分析。通过 LPS 刺激后 TNF-α 的定量来评估 TLR-4 多态性在对照样本中的功能。还通过流式细胞术分析 TLR-4 和 TLR-2 的表达。
TLR-4 多态性存在于 8.5%的肾移植患者中。这种多态性与 TNF-α分泌受损有关。一般来说，在肾移植患者中，单核细胞和中性粒细胞中的 TLR-4 表达低于健康志愿者。健康志愿者中 TLR-2 和 TLR-4 的表达在 A299G/T399I TLR-4 多态性患者中高于野生型基因型健康志愿者（p<0.01 和 p<0.05），也高于 A299G/T399I TLR-4 多态性肾移植患者（p<0.05）。野生型基因型肾移植患者中性粒细胞中的 TLR-2 表达高于野生型基因型健康志愿者，也高于 A299G/T399I 肾移植患者（p<0.01）。
稳定的肾移植患者携带 TLR-4 多态性，外周单核细胞中 TLR-4 和 TLR-2 受体的表达较低，这最终表明对警报素的反应性较低。
