NF-κB activation precedes increases in mRNA encoding neurokinin-1 receptor, proinflammatory cytokines, and adhesion molecules in dextran sulfate sodium-induced colitis in rats
NF-κB activation precedes increases in mRNA encoding neurokinin-1 receptor, proinflammatory cytokines, and adhesion molecules in dextran sulfate sodium-induced colitis in rats
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DOI：
10.1007/s10620-005-3066-y
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发表时间：
2005-12-01
影响因子：
3.1
通讯作者：
Becker, JM
中科院分区：
文献类型：
--
作者：
Reed, KL;Fruin, AB;Becker, JM
核因子-kappaB在引发结肠炎相关炎症中起着关键作用。采用大鼠DSS结肠炎模型，研究P物质(SP)、神经激肽-1受体(NK-1R)、促炎细胞因子和黏附分子表达与核因子-kappaB活化的时间关系。大鼠在水中加入5%DSS，每日处死，连续6天。观察结肠组织学变化、核因子-kappaB活性、髓过氧化酶(MPO)活性、NK-1R、SP、TNF-α、IL-1β、VCAM-1、ICAM-1、E-选择素、CINC-1、MIP-1α和iNOS的表达。核因子-kappaB的活性在第1天呈双相性增加，在第4-6天再次增加。ICAM-1、CINC-1、IL-1β、肿瘤坏死因子α、血管细胞黏附分子-1和NK-1R的mRNA水平在2-4天时显著升高(P<0.05)。INOS mRNA水平、MPO活性和粘膜损伤在第6天出现升高。这些数据表明，核因子-kappaB的激活基本上先于生理疾病症状和活动性炎症的开始。
Nuclear factor kappa B (NF-kappa B) plays a key role in initiating inflammation associated with colitis. A systematic study was conducted in the rat DSS colitis model to determine the temporal relationship between NF-kappa B activation and expression of substance P (SP), neurokinin-1 receptor (NK-1R), proinflammatory cytokines, and adhesion molecules. Rats were given 5% DSS in their water and sacrificed daily for 6 days. Colon tissue was collected for assessment of histological changes, NF-kappa B activation, myeloperoxidase (MPO) activity, and expression of NK-1R, SP, TNF alpha, IL-1 beta, VCAM-1, ICAM-1, E-selectin, CINC-1, MIP-1 alpha, and iNOS. NF-kappa B activation increased, biphasically, on Day 1 and again on Days 4-6. The mRNA levels for ICAM-1, CINC- 1, IL-1 beta, TNF alpha, VCAM-1, and NK-1R rose significantly (P < 0.05) by 2-4 days. Increased iNOS mRNA levels, MPO activity, and mucosal damage occurred on Day 6. These data demonstrate that NF-kappa B activation substantially precedes the onset of physical disease signs and active inflammation.