Impaired IgG production in mice deficient for heat shock transcription factor 1
Impaired IgG production in mice deficient for heat shock transcription factor 1
复制标题
DOI：
10.1074/jbc.m405986200
复制
发表时间：
2004-09-10
影响因子：
4.8
通讯作者：
Nakai, A
中科院分区：
文献类型：
--
作者：
Inouye, S;Izu, H;Nakai, A
热休克因子1（HSF 1）是热休克反应中热休克蛋白的主要反式激活因子，也参与卵子发生、精子发生和胎盘发育。然而，我们不知道控制发育过程的分子机制。在这项研究中，我们发现，HSF 1基因敲除小鼠表现出T细胞依赖性B细胞反应的显着下降。当用绵羊红细胞腹腔免疫小鼠时，在免疫后6天，HSF 1-null小鼠中的绵羊红细胞特异性IgG产生，特别是IgG 2a产生比野生型小鼠低约50%，而IgM产生是正常的。溴脱氧尿苷掺入免疫HSF 1-null小鼠的脾细胞的数量是三分之一，在免疫野生型小鼠，表明脾细胞的增殖减少。我们分析了脾细胞和腹腔巨噬细胞中细胞因子和趋化因子的水平与脂多糖和干扰素-γ刺激，发现白细胞介素-6和CCL 5的表达水平显着低于HSF 1-null细胞比野生型细胞。此外，我们证明了IL-6基因是HSF 1的直接靶基因。这些结果揭示了HSF 1与免疫反应和炎症相关基因之间的新分子联系。
Heat shock factor 1 (HSF1) is a major transactivator of heat shock proteins in response to heat shock, and it is also involved in oogenesis, spermatogenesis, and placental development. However, we do not know the molecular mechanisms controlling developmental processes. In this study, we found that HSF1-null mice exhibited a significant decrease in the T cell-dependent B cell response. When mice were immunized intraperitoneally with sheep red blood cells, the sheep red blood cell-specific IgG production, especially IgG2a production, in HSF1-null mice was about 50% lower than that in wildtype mice at 6 days after the immunization, whereas IgM production was normal. The number of bromodeoxyuridine-incorporated spleen cells in immunized HSF1-null mice was one-third that in immunized wild-type mice, indicating reduced proliferation of the spleen cells. We analyzed levels of cytokines and chemokines in spleen cells and in peritoneal macrophages stimulated with lipopolysaccharide and interferon-gamma and found that expression levels of interleukin-6 and CCL5 were significantly lower in HSF1-null cells than those in wild-type cells. Furthermore, we demonstrated that the IL-6 gene is a direct target gene of HSF1. These results revealed a novel molecular link between HSF1 and a gene related to immune response and inflammation.