Kim Jin-A, Choi Suck-Chei, Yun Ki-Jung, Kim Dae-Ki, Han Myung-Kwan, Seo Geom-Seog, Yeom Ju-Jin, Kim Tae-Hyun, Nah Yong-Ho, Lee Young-Mi
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University School of Medicine, Iksan, Chonbuk, South Korea.
Inflamm Bowel Dis. 2003 Jul;9(4):224-9. doi: 10.1097/00054725-200307000-00002.
Although tryptase released from mast cells might play a key role in the pathogenesis of ulcerative colitis (UC), the role of protease-activated receptor 2 (PAR2), tryptase receptor, remains unclear in the pathogenesis of this disease. The expressions of PAR2 and tumor necrosis factor (TNF) alpha in nine UC tissues and nine normal tissues were examined by immunohistochemistry. TNF-alpha levels secreted from human leukemic mast cell line (HMC-1) after the treatment of PAR2 agonists were also measured by enzyme-linked immunosorbent assay. The PAR2 and TNF-alpha proteins were more significantly detectable in UC tissues than in normal tissues. Furthermore, 65.2% of PAR2+ cells and 66.4% of TNF-alpha+ cells in UC tissues were tryptase-positive cells. In other words, 60.6% and 46.3% of tryptase-positive cells in UC tissues were PAR2+ cells and TNF-alpha+ cells, respectively. A chi2 analysis showed correlation (p < 0.007) between PAR2 and TNF-alpha in tryptase-positive mast cells. Moreover, PAR2 agonists significantly induced the TNF-alpha secretion from HMC-1. These results indicate that the activation of the mast cells through PAR2 may be involved in the pathogenesis of UC.
尽管肥大细胞释放的类胰蛋白酶可能在溃疡性结肠炎(UC)的发病机制中起关键作用,但蛋白酶激活受体2(PAR2)即类胰蛋白酶受体在该疾病发病机制中的作用仍不清楚。通过免疫组织化学检测了9个UC组织和9个正常组织中PAR2和肿瘤坏死因子(TNF)α的表达。还通过酶联免疫吸附测定法测量了用PAR2激动剂处理后人白血病肥大细胞系(HMC-1)分泌的TNF-α水平。与正常组织相比,UC组织中PAR2和TNF-α蛋白的可检测性更显著。此外,UC组织中65.2%的PAR2+细胞和66.4%的TNF-α+细胞是类胰蛋白酶阳性细胞。换句话说,UC组织中60.6%和46.3%的类胰蛋白酶阳性细胞分别是PAR2+细胞和TNF-α+细胞。卡方分析显示类胰蛋白酶阳性肥大细胞中PAR2与TNF-α之间存在相关性(p<0.007)。此外,PAR2激动剂显著诱导HMC-1分泌TNF-α。这些结果表明,通过PAR2激活肥大细胞可能参与UC的发病机制。