Rojas-Cartagena Carmencita, Flores Idhaliz, Appleyard Caroline B
Department of Microbiology, Ponce School of Medicine, Ponce, PR 00732-7004, USA.
Cytokine. 2005 Oct 21;32(2):85-93. doi: 10.1016/j.cyto.2005.08.001. Epub 2005 Oct 5.
TNF-alpha is known to play an important role in inflammatory bowel disease (IBD); however, the pathophysiological role of its receptors is still under study. Acute colitis was induced in rats by intracolonic administration of trinitrobenzene sulfonic acid (TNBS). Control rats received the ethanol vehicle. Rats were sacrificed 72 h later and samples of tissue and fluids were collected. There was a significant increase in the protein levels of sTNF-alpha, sTNFRI, and sTNFRII in the peritoneal fluid (PF) of experimental rats. TNF-alpha, TNFRI, and TNFRII mRNA expression was increased significantly in the colon of experimental animals compared to controls. TRAF3 and TRAF5 expression was also significantly higher, as was that of the adhesion molecules ICAM-1 and E-selectin. The increased expression of TNF-alpha, TNFRs, and the associated signaling factors in the colon of this rat model of IBD provides further evidence for their involvement in the promotion of inflammation and tissue damage. In addition, increased levels of sTNFRs in the PF of experimental rats--particularly sTNFRII--may be involved in the development of colitis by serving as a reservoir of TNF-alpha, and thus provide a novel therapeutic target for IBD.
已知肿瘤坏死因子-α（TNF-α）在炎症性肠病（IBD）中发挥重要作用；然而，其受体的病理生理作用仍在研究中。通过向大鼠结肠内注射三硝基苯磺酸（TNBS）诱导急性结肠炎。对照大鼠接受乙醇载体。72小时后处死大鼠并收集组织和液体样本。实验大鼠腹腔液（PF）中可溶性TNF-α（sTNF-α）、可溶性TNF受体I（sTNFRI）和可溶性TNF受体II（sTNFRII）的蛋白水平显著升高。与对照相比，实验动物结肠中TNF-α、TNFRI和TNFRII的mRNA表达显著增加。肿瘤坏死因子受体相关因子3（TRAF3）和肿瘤坏死因子受体相关因子5（TRAF5）的表达也显著更高，黏附分子细胞间黏附分子-1（ICAM-1）和E-选择素的表达也是如此。在该IBD大鼠模型的结肠中，TNF-α、TNF受体及相关信号因子表达增加，为它们参与促进炎症和组织损伤提供了进一步证据。此外，实验大鼠PF中sTNFRs水平升高——尤其是sTNFRII——可能通过作为TNF-α的储存库而参与结肠炎的发展，从而为IBD提供了一个新的治疗靶点。
