The RD1 locus in the Mycobacterium tuberculosis genome contributes to the maturation and secretion of IL-1α from infected macrophages through the elevation of cytoplasmic calcium levels and calpain activation.
The RD1 locus in the Mycobacterium tuberculosis genome contributes to the maturation and secretion of IL-1α from infected macrophages through the elevation of cytoplasmic calcium levels and calpain activation.
复制标题
结核分枝杆菌基因组中的 RD1 位点通过提高细胞质钙水平和激活钙蛋白酶，促进受感染巨噬细胞成熟和分泌 IL-1α。
DOI：
10.1111/2049-632x.12075
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kawamura I.
中科院分区：
文献类型：
--
作者：
Yang R;Xi C;Sita DR;Sakai S;Tsuchiya K;Hara H;Shen Y;Qu H;Fang R;Mitsuyama M;Kawamura I.
差异区域 1 (RD1) 是结核分枝杆菌基因组中的一个基因组位点，已被证明参与细菌的毒力、诱导细胞死亡以及感染巨噬细胞中的细胞因子分泌。在这项研究中，我们研究了 RD1 在白细胞介素 1α (IL-1α) 分泌中的作用。结核病 H37Rv 菌株，但不是 RD1 (ΔRD1) 缺陷的突变菌株，显着诱导受感染巨噬细胞分泌 IL-1α。虽然仅在 H37Rv 感染的巨噬细胞中观察到 IL-1α 分泌，但感染 H37Rv 和 ΔRD1 后，IL-1α 转录和 pro-IL1α 合成水平没有差异。有趣的是，ΔRD1 感染不会增加细胞内 Ca2+ 水平，并且 Ca2+ 螯合剂显着抑制 H37Rv 感染后的 IL-1α 分泌。此外，通过钙离子载体 A23187 处理，可以恢复 ΔRD1 诱导 IL-1α 分泌的能力。在感染 H37Rv 的巨噬细胞中检测到钙蛋白酶活性显着增加，但感染 ΔRD1 的巨噬细胞则没有，并且钙蛋白酶抑制剂消除了 IL-1α 的分泌。综上所述，这些结果表明 inM。在结核感染的巨噬细胞中，RD1 通过增强 Ca2+ 的流入以及随后的钙蛋白酶激活来促进 IL-1α 的成熟和分泌。
Region of difference 1 (RD1) is a genomic locus in theMycobacterium tuberculosisgenome that has been shown to participate in the virulence of the bacterium, induction of cell death, and cytokine secretion in infected macrophages. In this study, we investigated the role of RD1 in interleukin-1α (IL-1α) secretion.M. tuberculosisH37Rv strain, but not a mutant strain deficient for RD1 (∆RD1), significantly induced IL-1α secretion from infected macrophages. Although IL-1α secretion was only observed in H37Rv-infected macrophages, there was no difference in the level of IL-1α transcription and pro-IL1α synthesis after infection with H37Rv and ∆RD1. Interestingly, ∆RD1 infection did not increase intracellular Ca2+levels, and Ca2+chelators markedly inhibited IL-1α secretion in response to H37Rv infection. Moreover, the inability of ∆RD1 to induce IL-1α secretion was restored by treatment with the calcium ionophore A23187. A significant increase in calpain activity was detected in macrophages infected with H37Rv, but not with ∆RD1, and calpain inhibitors abrogated IL-1α secretion. Taken together, these results suggest that inM. tuberculosis-infected macrophages, RD1 contributed to maturation and secretion of IL-1α by enhancing the influx of Ca2+followed by calpain activation.