Department of Clinical Immunology and Rheumatology, Christian Medical College, Tamil Nadu, Vellore, 632004, India.
Rheumatol Int. 2022 Mar;42(3):535-543. doi: 10.1007/s00296-020-04785-0. Epub 2021 Feb 2.
Toll-like receptors (TLR) 4 and its endogenous ligands are highly expressed in aorta. In the present study, we have explored the effect of TLR-4 activation by pro-inflammatory and angiogenic factors in PBMCs of patients with Takayasu Arteritis (TA). In the screening cohort, PBMCs of TA (n = 6) and healthy controls (n = 6) were stimulated with LPS and cultured. mRNA expression of 84 genes were quantitated by RT2 Profiler™ PCR Array kit in PBMCs. Validation set of additional PBMCs from TA (n = 7) and healthy controls [HC) (n = 7) were then stimulated with LPS to study expression of selected genes with delta Ct > 0.1 in the screening cohort. Significant gene expressions were correlated with Indian Takayasu arteritis activity scores (ITAS 2010). Increased expression of CCL2 was observed only in unstimulated PBMCs of patients with TA [median relative difference (RD) of 2.37] as compared to HC (RD 1.37, p < 0.03) in validation cohort, while stimulation with TLR4 ligand led to increased mRNA expression of IL-1β (RD 7.9, p < 0.028) and IL-1R2 (RD 0.08 p < 0.013) genes as compared to that of HC [RD of 5.32 for IL-1β and 0.01 for IL-1R2, respectively] in validation cohort. TLR4 activation also led to significantly higher expression of HPSE, TIMP1 and low expression of VEGFB, S1PR1, SERPINF1, ANGPLT4, ANGPT2, TIE1 and NOS3 genes in the screening cohort. But expression of VEGFB was not significant in validation cohort. The significant gene expressions, however, did not correlate with ITAS [ITAS2010 and ITAS-A (CRP)]. TLR4 activation leads to increased expression of IL-1β and IL-1R2 genes in PBMCs of patients with TA.
Toll 样受体（TLR）4 及其内源性配体在主动脉中高度表达。在本研究中，我们探讨了促炎和血管生成因子激活 TLR-4 对 Takayasu 动脉炎（TA）患者 PBMC 的影响。在筛选队列中，用 LPS 刺激 TA（n=6）和健康对照（n=6）的 PBMC 并进行培养。通过 RT2 Profiler™PCR 阵列试剂盒定量检测 PBMC 中 84 个基因的 mRNA 表达。然后用 LPS 刺激来自 TA（n=7）和健康对照[HC）（n=7）的额外 PBMC 的验证集，以研究在筛选队列中 delta Ct>0.1 的选定基因的表达。显著的基因表达与印度 Takayasu 动脉炎活动评分（ITAS 2010）相关。仅在 TA 患者未刺激的 PBMC 中观察到 CCL2 的表达增加[与 HC 相比，中位数相对差异（RD）为 2.37]（RD 1.37，p<0.03），而 TLR4 配体刺激导致 IL-1β（RD 7.9，p<0.028）和 IL-1R2（RD 0.08，p<0.013）基因的 mRNA 表达增加与 HC 相比[IL-1β 的 RD 为 5.32，IL-1R2 的 RD 为 0.01]在验证队列中。TLR4 激活还导致 HPSE、TIMP1 的表达显著升高，VEGFB、S1PR1、SERPINF1、ANGPLT4、ANGPT2、TIE1 和 NOS3 基因的表达显著降低在筛选队列中。但是，VEGFB 的表达在验证队列中并不显著。然而，这些显著的基因表达与 ITAS 无关[ITAS2010 和 ITAS-A（CRP）]。TLR4 激活导致 TA 患者 PBMC 中 IL-1β 和 IL-1R2 基因的表达增加。
