The novel cytokine interleukin-33 activates acinar cell proinflammatory pathways and induces acute pancreatic inflammation in mice.
The novel cytokine interleukin-33 activates acinar cell proinflammatory pathways and induces acute pancreatic inflammation in mice.
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新型的细胞因子白介素-33激活腺泡细胞促炎途径并诱导小鼠急性胰腺炎症。
DOI：
10.1371/journal.pone.0056866
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Samuel I
中科院分区：
文献类型：
--
作者：
Kempuraj D;Twait EC;Williard DE;Yuan Z;Meyerholz DK;Samuel I
急性胰腺炎可能致命，但由于对疾病发病机制知之甚少，治疗选择有限。 IL-33 是一种新型 IL-1 细胞因子家族成员，在多种炎症性疾病中发挥作用，但其在急性胰腺炎中的作用尚不清楚。具体而言，胰腺腺泡细胞在应激时是否产生IL-33或对IL-33刺激作出反应，以及IL-33是否加剧急性胰腺炎症尚不清楚。在导管结扎诱导的小鼠和大鼠急性胰腺炎中，我们发现（a）胰腺中IL-33浓度增加； (b) 肥大细胞分泌IL-33并对IL-33做出反应，在胰腺和肺中显示出脱颗粒； (c)血浆组胺和胰物质P浓度增加； (d)胰腺和肺促炎细胞因子浓度增加。在分离的小鼠胰腺腺泡细胞中，TNF-α刺激增加了IL-33的释放，而IL-33刺激增加了促炎细胞因子的释放，两者都涉及ERK MAP激酶途径；类黄酮木犀草素抑制 IL-33 刺激的 IL-6 和 CCL2/MCP-1 释放。在未结扎导管的小鼠中，给予外源性 IL-33 诱导胰腺炎症，但没有肥大细胞脱颗粒或空肠炎症；胰腺变化包括多灶性水肿和血管周围中性粒细胞和一些巨噬细胞浸润。在接受外源性 IL-33 的小鼠胰腺中，ERK MAP 激酶（但不是 p38 或 JNK）和 NF-kB 亚基 p65 被激活，从这些小鼠胰腺中分离出的腺泡细胞显示出自发细胞因子释放增加（IL-6、CXCL2/MIP-2α）。此外，IL-33 还可激活人胰腺组织中的 ERK。由于外源性 IL-33 不会在诱导胰腺炎症的小鼠中诱导空肠炎症，因此我们发现了 IL-33/腺泡细胞轴在中性粒细胞和巨噬细胞的募集以及急性胰腺炎症恶化中的潜在作用。 IL-33 在急性胰腺炎中被诱导，激活腺泡细胞促炎途径并加剧急性胰腺炎症。
Acute pancreatitis is potentially fatal but treatment options are limited as disease pathogenesis is poorly understood. IL-33, a novel IL-1 cytokine family member, plays a role in various inflammatory conditions but its role in acute pancreatitis is not well understood. Specifically, whether pancreatic acinar cells produce IL-33 when stressed or respond to IL-33 stimulation, and whether IL-33 exacerbates acute pancreatic inflammation is unknown. In duct ligation-induced acute pancreatitis in mice and rats, we found that (a) IL-33 concentration was increased in the pancreas; (b) mast cells, which secrete and also respond to IL-33, showed degranulation in the pancreas and lung; (c) plasma histamine and pancreatic substance P concentrations were increased; and (d) pancreatic and pulmonary proinflammatory cytokine concentrations were increased. In isolated mouse pancreatic acinar cells, TNF-α stimulation increased IL-33 release while IL-33 stimulation increased proinflammatory cytokine release, both involving the ERK MAP kinase pathway; the flavonoid luteolin inhibited IL-33-stimulated IL-6 and CCL2/MCP-1 release. In mice without duct ligation, exogenous IL-33 administration induced pancreatic inflammation without mast cell degranulation or jejunal inflammation; pancreatic changes included multifocal edema and perivascular infiltration by neutrophils and some macrophages. ERK MAP kinase (but not p38 or JNK) and NF-kB subunit p65 were activated in the pancreas of mice receiving exogenous IL-33, and acinar cells isolated from the pancreas of these mice showed increased spontaneous cytokine release (IL-6, CXCL2/MIP-2α). Also, IL-33 activated ERK in human pancreatic tissue. As exogenous IL-33 does not induce jejunal inflammation in the same mice in which it induces pancreatic inflammation, we have discovered a potential role for an IL-33/acinar cell axis in the recruitment of neutrophils and macrophages and the exacerbation of acute pancreatic inflammation. IL-33 is induced in acute pancreatitis, activates acinar cell proinflammatory pathways and exacerbates acute pancreatic inflammation.
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影响因子：
24.5
作者：
Johnson, CD;Abu-Hilal, M
通讯作者：
Abu-Hilal, M
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DOI：
10.1016/j.bbrc.2009.06.008
发表时间：
2009-08-14
影响因子：
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作者：
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