Interleukin-34 sustains inflammatory pathways in the gut
Interleukin-34 sustains inflammatory pathways in the gut
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DOI：
10.1042/cs20150132
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发表时间：
2015-08-01
期刊：
影响因子：
6
通讯作者：
Monteleone, Giovanni
中科院分区：
文献类型：
--
作者：
Franze, Eleonora;Monteleone, Ivan;Monteleone, Giovanni
IBD（炎症性肠病）相关的组织损伤发生在单核细胞/巨噬细胞大量浸润的区域。这些细胞对炎性刺激物的反应是增加细胞因子/趋化因子的产生。在本研究中，我们分析了IL（白细胞介素）-34，单核细胞/巨噬细胞分化，存活和功能的调节剂，在IBD中的表达和作用。CD（克罗恩病）和UC（溃疡性结肠炎）患者的炎症粘膜中IL-34 mRNA和蛋白表达显著增加，与相同患者和正常对照的未受累区域相比。IL-34在TNF-α（肿瘤坏死因子α）和TLR（Toll样受体）配体从正常结肠分离的LPMC（固有层单核细胞）中上调，在IBD患者的肠活检和LPMC中下调。用IL-34处理正常LPMC以ERK 1/2（细胞外信号调节激酶1/2）依赖性方式增加TNF-α表达，并且IBD粘膜外植体中IL-34的中和减少TNF-α和IL-6合成。总之，我们的研究结果表明，IL-34在IBD中上调，并表明这种细胞因子在维持这种疾病的炎症反应中的作用。
IBD (inflammatory bowel disease)-related tissue damage occurs in areas which are massively infiltrated with monocytes/macrophages. These cells respond to inflammatory stimuli with enhanced production of cytokines/chemokines. In the present study, we analysed the expression and role of IL (interleukin)-34, a regulator of monocyte/macrophage differentiation, survival and function, in IBD. A significant increase in IL-34 mRNA and protein expression was seen in inflamed mucosa of patients with CD (Crohn's disease) and patients with UC (ulcerative colitis) compared with the uninvolved areas of the same patients and normal controls. IL-34 was up-regulated in LPMCs (lamina propria mononuclear cells) isolated from normal colon by TNF-alpha (tumour necrosis factor alpha) and TLR (Toll-like receptor) ligands and was down-regulated in intestinal biopsies and LPMCs of IBD patients upon treatment with infliximab. Treatment of normal LPMCs with IL-34 increased TNF-alpha expression in an ERK1/2 (extracellular-signal-regulated kinase 1/2)-dependent fashion and neutralization of IL-34 in IBD mucosal explants reduced TNF-alpha and IL-6 synthesis. In conclusion, our results indicate that IL-34 is up-regulated in IBD and suggest a role for this cytokine in sustaining the inflammatory responses in this disease.