Expression of Tumor Necrosis Factor-&agr;, Interleukin-6, and Interferon-&ggr; in Spontaneous Chronic Pancreatitis in the WBN/Kob Rat

Expression of Tumor Necrosis Factor-&agr;, Interleukin-6, and Interferon-&ggr; in Spontaneous Chronic Pancreatitis in the WBN/Kob Rat
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肿瘤坏死因子的表达-

DOI:
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发表时间:
2001
期刊:
影响因子:
--
通讯作者:
N. Sawabu
N. Sawabu
中科院分区:
--
文献类型:
--
作者:
M. Xie;Y. Motoo;S. Su;N. Sawabu

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为了阐明细胞因子在慢性胰腺炎(CP)中的病理生理学意义,我们分析了WBN/Kob大鼠自发性CP发病和进展中各种细胞因子的组织表达。4周龄雄性WBN/Kob大鼠饲喂特殊颗粒饲料(MB-3)20周,每4周处死6只大鼠。病理上,CP发生在12周,此后进展。炎症和纤维化分别在12周和16周达到高峰。通过半定量逆转录聚合酶链反应,肿瘤坏死因子(TNF)-,白细胞介素(IL)-6,和干扰素(IFN)-mRNA的表达分别在8周,12周和16周达到峰值。&agr;&ggr;免疫组化显示IL-6在浸润的炎性细胞和血管内皮细胞中表达,而TNF-α在腺泡和浸润细胞中表达。&agr; IFN-γ定位于腺泡、浸润和导管细胞,其表达强度与纤维化、Ⅲ型胶原和平滑肌肌动蛋白的表达强度呈显著相关。&ggr;&agr;原位杂交结果与RT-PCR结果一致。这些结果表明,TNF-α和IL-6的组织表达参与了胰腺炎的发病,IFN-α的表达与CP的进展有关。&agr;&ggr;
To clarify the pathophysiological significance of cytokines in chronic pancreatitis (CP), we analyzed tissue expressions of various cytokines in the onset and progression of spontaneous CP in the WBN/Kob rat. Four-week-old male WBN/Kob rats were fed a special pellet diet (MB-3) for 20 weeks, and 6 rats were killed every 4 weeks. Pathologically, CP occurred at 12 weeks and progressed thereafter. The inflammation and fibrosis peaked at 12 and 16 weeks, respectively. By semiquantitative reverse transcription-polymerase chain reaction, the expression of tumor necrosis factor (TNF)-&agr;, interleukin (IL)-6, and interferon (IFN)-&ggr; mRNAs peaked at 8, 12, and 16 weeks, respectively. Immunohistochemistry showed IL-6 expression in infiltrating inflammatory cells and vascular endothelial cells, whereas TNF-&agr; was expressed in both acinar and infiltrating cells. IFN-&ggr; was localized to acinar, infiltrating and ductal cells, and its expression intensity showed significant correlation with those of fibrosis, type III collagen and &agr;-smooth muscle actin. The in situ hybridization results were consistent with the RT-PCR data. These results suggest that tissue expressions of TNF-&agr; and IL-6 are involved in the onset of pancreatitis and that IFN-&ggr; expression is related to the progression of CP.
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