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首页> 外文期刊>Cytokine >IL-33 mast cell axis is central in LL-37 induced bladder inflammation and pain in a murine interstitial cystitis model
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IL-33 mast cell axis is central in LL-37 induced bladder inflammation and pain in a murine interstitial cystitis model

机译：IL-33蜂窝轴是LL-37诱导的膀胱炎症和鼠中疼痛中的中央肿瘤性炎症模型

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Interstitial cystitis (IC), also known as painful bladder syndrome (PBS), is a debilitating chronic condition that afflicts over 3 million women above the age of 18 in the U.S., and most patients fail to respond to current treatment options. Mast cells have previously been implicated as both a diagnostic and prognostic marker in IC/PBS. Patients with IC/PBS have been shown to have elevated levels of IL-33, a cytokine released in response to tissue insult, in their urine. We hypothesize that mast cell-mediated inflammation induced from IL-33 may play an important role in initiating pain and inflammation in IC/PBS. A human cathelicidin, LL-37, which is found at elevated levels in IC/PBS patients, was used to induce an IC/PBS-like state of inflammation and bladder pain in mast cell deficient C-kit (?/?) and wild type C57Bl/6 (WT) mice. Inflammation was quantified using myeloperoxidase (MPO) expression in bladder tissues measured via ELISA. Response rate to suprapubic stimulation from von Frey filaments was used to assess the relative pain and discomfort. Both types of mice increased IL-33 expression in response to LL-37 exposure. However, mast cell deficient mice demonstrated significantly lower levels of inflammation (p?
机译：间质膀胱炎（IC），也称为痛苦的膀胱综合征（PBS），是一种衰弱的慢性病症，患有18岁以上的300多万女性，大多数患者未能应对当前的治疗方案。以前已经将肥大细胞涉及IC / PBS中的诊断和预后标志物。 IC / PBS的患者已被证明具有升高的IL-33水平，一种释放的细胞因子，以应对组织损伤，在尿液中释放。我们假设从IL-33诱导的肥大细胞介导的炎症可能在IC / PBS中引发疼痛和炎症来发挥重要作用。在IC / PBS患者升高的水平下发现的人类疗法素LL-37用于诱导IC / PBS样状态的炎症和膀胱疼痛的肥大细胞缺乏C-kit（？/？）和野生键入C57BL / 6（WT）小鼠。通过ELISA测量的膀胱组织中的髓氧化酶（MPO）表达量化炎症。从von Frey丝丝素刺激的反应率用于评估相对疼痛和不适。两种类型的小鼠响应于LL-37暴露而增加IL-33表达。然而，与WT小鼠相比，肥大细胞缺陷小鼠显着降低炎症（p≤0.001）和减少疼痛反应（p≤0.001）。这些发现涉及IL-33桅杆细胞依赖性轴，潜在的IC / PBS中的疼痛和炎症的病因。旨在靶向IL-33 - 肥大细胞轴的未来治疗剂可能是治疗IC / PBS的有用靶标。

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