Secretory leukocyte protease inhibitor suppresses the inflammation and joint damage of bacterial cell wall-induced arthritis
Secretory leukocyte protease inhibitor suppresses the inflammation and joint damage of bacterial cell wall-induced arthritis
复制标题
分泌型白细胞蛋白酶抑制剂可抑制细菌细胞壁诱发的关节炎的炎症和关节损伤
DOI：
10.1084/jem.190.4.535
复制
发表时间：
1999-08-16
影响因子：
15.3
通讯作者：
Wahl, SM
中科院分区：
文献类型：
--
作者：
Song, XY;Zeng, L;Wahl, SM
蛋白酶和蛋白酶抑制剂之间平衡的破坏通常与病理组织破坏有关。为了探索分泌性白细胞蛋白酶抑制剂 (SLPI) 在糜烂性关节疾病中的治疗潜力，我们对活性大鼠 SLPI 进行了克隆、测序和表达，它与人类 SLPI 中发现的蛋白酶反应位点相同。在大鼠链球菌细胞壁 (SCW) 诱导的炎性糜烂性多关节炎模型中，发炎关节组织中内源性 SLPI 的 mRNA 和蛋白质水平出人意料地上调。纯化的重组大鼠 SLPI 的全身递送抑制了关节炎症以及软骨和骨破坏。在急性和慢性关节炎中，通过 SLPI 治疗，循环肿瘤坏死因子 α 和核因子 κ B 激活所反映的炎症通路以及通过 II 型胶原酶生成裂解产物的循环水平检测到的软骨吸收所反映的炎症通路均被减弱，表明 SLPI 的作用可能超出了丝氨酸蛋白酶的抑制范围。
Disruption of the balance between proteases and protease inhibitors is often associated with pathologic tissue destruction. To explore the therapeutic potential of secretory leukocyte protease inhibitor (SLPI) in erosive joint diseases, we cloned, sequenced, and expressed active rat SLPI, which shares the protease-reactive site found in human SLPI. In a rat streptococcal cell wall (SCW)-induced model of inflammatory erosive polyarthritis, endogenous SLPI was unexpectedly upregulated at both mRNA and protein levels in inflamed joint tissues. Systemic delivery of purified recombinant rat SLPI inhibited joint inflammation and cartilage and bone destruction. Inflammatory pathways as reflected by circulating tumor necrosis factor alpha and nuclear factor kappa B activation and cartilage resorption detected by circulating levels of type II collagen collagenase-generate cleavage products were all diminished by SLPI treatment in acute and chronic arthritis, indicating that the action of SLPI may extend beyond inhibition of serine proteases.