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首页> 外文期刊>Infection and immunity >Distinct Compartmentalization of NF-κB Activity in Crypt and Crypt-Denuded Lamina Propria Precedes and Accompanies Hyperplasia and/or Colitis following Bacterial Infection
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Distinct Compartmentalization of NF-κB Activity in Crypt and Crypt-Denuded Lamina Propria Precedes and Accompanies Hyperplasia and/or Colitis following Bacterial Infection

机译：细菌感染后，在隐窝和隐窝剥脱的固有层中NF-κB活性明显区分开，并伴有增生和/或结肠炎

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Citrobacter rodentium induces transmissible murine colonic hyperplasia (TMCH) and variable degrees of inflammation and necrosis depending upon the genetic background. Utilizing C. rodentium-induced TMCH in C3H/HeNHsd inbred mice, we observed significant crypt hyperplasia on days 3 and 7 preceding active colitis. NF-κB activity in the crypt-denuded lamina propria (CLP) increased within 24 h postinfection, followed by its activation in the crypts at day 3, which peaked by day 7. Increases in interleukin-α1 (IL-1α), IL-12(p40), and macrophage inflammatory protein 1α (MIP-1α) paralleled NF-κB activation, while increases in IL-1α/β, IL-6/IL-12(p40)/granulocyte colony-stimulating factor (G-CSF)/keratinocyte-derived chemokine (KC)/monocyte chemotactic protein 1 (MCP-1), and MIP-1α followed NF-κB activation leading to significant recruitment of neutrophils to the colonic mucosa and increased colonic myeloperoxidase (MPO) activity. Phosphorylation of the crypt cellular and nuclear p65 subunit at serines 276 and 536 led to functional NF-κB activation that facilitated expression of its downstream target, CXCL-1/KC, during TMCH. Distinct compartmentalization of phosphorylated extracellular signal-regulated kinase 1 and 2 ([ERK1/2] Thr180/Tyr182) and p38 (Thr202/Tyr204) in the CLP preceded increases in the crypts. Inhibition of ERK1/2 and p38 suppressed NF-κB activity in both crypts and the CLP. Dietary administration of 6% pectin or 4% curcumin in C. rodentium-infected mice also inhibited NF-κB activity and blocked CD3, F4/80, IL-1α/β, G-CSF/MCP-1/KC, and MPO activity in the CLP while not affecting NF-κB activity in the crypts. Thus, distinct compartmentalization of NF-κB activity in the crypts and the CLP regulates crypt hyperplasia and/or colitis, and dietary intervention may be a novel strategy to modulate NF-κB-dependent protective immunity to facilitate crypt regeneration following C. rodentium-induced pathogenesis.
机译：啮齿类柠檬酸杆菌可引起可传播的鼠结肠增生（TMCH），并根据遗传背景不同程度地引起炎症和坏死。在C3H / HeNHsd近交小鼠中利用C.rodentium诱导的TMCH，我们在活动性结肠炎发生的第3天和第7天观察到了明显的隐窝增生。隐窝固有层（CLP）中的NF-κB活性在感染后24小时内增加，随后在隐窝中被激活，在第3天达到峰值，并在第7天达到峰值。白介素-α1（IL-1α），IL- 12（p40）和巨噬细胞炎症蛋白1α（MIP-1α）与NF-κB激活平行，而IL-1α/β，IL-6 / IL-12（p40）/粒细胞集落刺激因子（G-CSF）增加）/角质形成细胞衍生的趋化因子（KC）/单核细胞趋化蛋白1（MCP-1）和MIP-1α跟随NF-κB活化，导致嗜中性白细胞大量募集到结肠粘膜并增加结肠髓过氧化物酶（MPO）活性。丝氨酸276和536的隐窝细胞和核p65亚基的磷酸化导致功能性NF-κB活化，从而促进了TMCH期间其下游靶标CXCL-1 / KC的表达。隐窝增加之前，CLP中磷酸化的细胞外信号调节激酶1和2（[ERK1 / 2] Thr180 / Tyr182）和p38（Thr202 / Tyr204）的明显区室化。抑制ERK1 / 2和p38可抑制隐窝和CLP中的NF-κB活性。日粮中6％的果胶或4％的姜黄素在感染了C.rodentium的小鼠中也抑制了NF-κB活性并阻断了CD3，F4 / 80，IL-1α/β，G-CSF / MCP-1 / KC和CLP中的MPO活性同时不影响隐窝中的NF-κB活性。因此，隐窝和CLP中的NF-κB活性的明显区室化调节了隐窝的增生和/或结肠炎，饮食干预可能是调节NF-κB依赖性保护性免疫以促进隐孢子虫诱导的隐窝再生的新策略。发病。

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