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半抗原诱导的大鼠复发性结肠炎症中细胞因子和黏附分子mRNA的模式

Pattern of cytokine and adhesion molecule mRNA in hapten-induced relapsing colon inflammation in the rat.

作者信息

Sun F F, Lai P S, Yue G, Yin K, Nagele R G, Tong D M, Krzesicki R F, Chin J E, Wong P Y

机构信息

Department of Cell Biology, School of Osteopathic Medicine, UMDNJ, Stratford, New Jersey 08084, USA.

出版信息

Inflammation. 2001 Feb;25(1):33-45. doi: 10.1023/a:1007023611478.

Abstract

We examined the mRNA expression of cytokines, chemokines, integrins, and selectins in colon lesions of rat colitis with a semi-quantitative RT-PCR assay. Rat colitis was induced by trinitrobenzene sulfonic acid (TNBS) in 50% ethanol. Within 24 h, an acute inflammation occurred with hyperemia, edema, necrosis and an intense infiltration of granulocytes in the mucosa. The lesion proceeded into a T-lymphocyte/monocyte-driven chronic inflammation for two weeks and healed in 6 weeks. An acute inflammation recurred at the same site when the recovered animals were systemically injected with TNBS. We isolated RNA from colon tissue at 24 h, 1, 2, 4, 6 weeks after TNBS treatment and from the relapsed animals. The mRNA for cytokines IL-1beta, IL-6, IL-10 and the chemokines CINC, MIP-1alpha, MCP-1 were significantly (P < 0.05) elevated and persisted for 2 weeks, decreased in 6 weeks and increased again during relapse. IFN-gamma mRNA stayed at control levels initially, but increased dramatically in the second weeks of chronic inflammation as well as in relapse. The mRNA levels of adhesion molecules, ICAM-1, VCAM-1, the mucosal homing integrin beta7 as well as P- and E-selectin were greatly enhanced between 1 and 3 weeks. The data showed that the chronically inflamed tissue expresses a time-dependent changing pattern of TH1 cytokines and adhesion molecules that maintain the infiltration and activation of inflammatory cells and tissue injury.

摘要

我们采用半定量逆转录聚合酶链反应(RT-PCR)分析法检测了大鼠结肠炎结肠病变中细胞因子、趋化因子、整合素和选择素的信使核糖核酸(mRNA)表达情况。用三硝基苯磺酸(TNBS)溶于50%乙醇诱导大鼠发生结肠炎。24小时内,黏膜出现急性炎症,伴有充血、水肿、坏死以及粒细胞的大量浸润。病变在两周内发展为T淋巴细胞/单核细胞驱动的慢性炎症,并在6周内愈合。当恢复的动物全身注射TNBS时,同一部位会再次出现急性炎症。我们在TNBS治疗后24小时、1周、2周、4周、6周以及复发动物的结肠组织中分离出RNA。细胞因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)以及趋化因子大鼠趋化因子(CINC)、巨噬细胞炎性蛋白-1α(MIP-1α)、单核细胞趋化蛋白-1(MCP-1)的mRNA显著升高(P<0.05)并持续2周,6周时下降,复发时再次升高。γ干扰素(IFN-γ)mRNA最初保持在对照水平,但在慢性炎症的第二周以及复发时急剧增加。黏附分子细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)、黏膜归巢整合素β7以及P-选择素和E-选择素的mRNA水平在1至3周内大幅升高。数据表明,慢性炎症组织表达TH1细胞因子和黏附分子的时间依赖性变化模式,这些模式维持了炎症细胞的浸润和激活以及组织损伤。

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