The Influence of LPS-Induced Maternal Inflammation on Postnatal Collagen-Induced Arthritis
The Influence of LPS-Induced Maternal Inflammation on Postnatal Collagen-Induced Arthritis
复制标题
脂多糖诱导的母体炎症对生后胶原诱导性关节炎的影响
DOI：
10.1007/s10753-018-0827-2
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发表时间：
2018-10-01
期刊：
影响因子：
5.1
通讯作者：
Sato, Kazuto
中科院分区：
文献类型：
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作者：
Imai, Atsuko;Fujimoto, Eka;Sato, Kazuto
母亲的健康和营养状况影响后代的健康和可能在他们身上发展的疾病。母体炎症从炎症反应和免疫改变的角度对子代的影响尚不完全清楚。我们假设母体炎症调节免疫和代谢功能，影响后代炎症性疾病的病理生理。本研究调查了母体炎症是否影响胶原诱导关节炎（CIA）的发病，CIA是一种人类类风湿关节炎的小鼠模型。雌性DBA/1J小鼠在受孕前5天单次腹腔注射脂多糖（LPS）。LPS处理的雄性后代被放置在母LPS组（MLG）。为了诱导CIA，用Freund's完全佐剂乳化II型胶原蛋白（CII），在13周和16周注射两次。在26周时处死子代，分析免疫和代谢参数。在CIA早期，MLG患者的关节肿胀程度低于对照组。从组织学分析来看，关节破坏的严重程度（关节炎评分的严重程度）和cii特异性IgG滴度在MLG中显著降低。然而，在26周时，血清白细胞介素(IL)-6水平（CIA疾病活动性指标）在MLG中显著升高。此外，MLG患者血清瘦素水平较低，且瘦素与血清IL-6呈负相关。总之，母体炎症不仅抑制炎症；它可能会延迟后代的CIA。26周时炎症细胞因子和瘦素浓度分析提示关节炎的病理生理恶化。这项研究还表明，母体炎症调节后代出生后的炎症反应模式。
Maternal health and nutritional status influence offspring health and the diseases that may develop in them. The effects of maternal inflammation on offspring from the perspective of the inflammatory response and immune changes are not fully understood. We hypothesized that maternal inflammation modulates immune and metabolic functions, affecting the pathophysiology of inflammatory diseases in offspring. This study investigated whether maternal inflammation affects the onset of collagen-induced arthritis (CIA), a murine model of human rheumatoid arthritis. Female DBA/1J mice received a single intraperitoneal injection of lipopolysaccharide (LPS) 5days before conception. Male offspring of LPS-treated dams were placed in the maternal LPS group (MLG). To induce CIA, type II collagen (CII) was emulsified with Freund's complete adjuvant and injected twice into each mouse, at 13 and 16weeks. The offspring were sacrificed at 26weeks to analyze immunological and metabolic parameters. The degree of joint swelling at an early stage of CIA was lower in the MLG than in the control group. From histological analysis, the severity of joint destruction (severity of arthritis score) and CII-specific IgG titer were significantly lower in the MLG. However, at 26weeks, serum interleukin (IL)-6 levels, an index of CIA disease activity, were significantly higher in the MLG. Moreover, serum leptin levels were lower in the MLG, and a negative correlation between leptin and serum IL-6 was observed. In conclusion, maternal inflammation does not merely suppress inflammation; it may delay CIA in offspring. The analysis of inflammatory cytokines and leptin concentrations at 26weeks suggests that the pathophysiology of arthritis was worsening. This study also suggests that maternal inflammation modulates postnatal inflammatory response patterns in offspring.