Secretory leucocyte protease inhibitor inhibits interferon-γ-induced cathepsin S expression
Secretory leucocyte protease inhibitor inhibits interferon-γ-induced cathepsin S expression
复制标题
DOI：
10.1074/jbc.m706884200
复制
发表时间：
2007-11-16
影响因子：
4.8
通讯作者：
McElvaney, Noel G.
中科院分区：
文献类型：
--
作者：
Geraghty, Patrick;Greene, Catherine M.;McElvaney, Noel G.
我们已经证明，与对照组相比，慢性阻塞性肺疾病患者的支气管肺泡灌洗液中含有更高水平的干扰素-γ。干扰素-γ是多种组织蛋白和基质金属蛋白酶的有效诱导剂。因此，我们推测在急、慢性肺部疾病中，干扰素-γ可以诱导巨噬细胞表达蛋白水解酶。慢性阻塞性肺疾病患者支气管肺泡灌洗液中组织蛋白酶S和基质金属蛋白酶-12水平较高。巨噬细胞与慢性阻塞性肺疾病支气管肺泡灌洗液孵育后，组织蛋白酶S和基质金属蛋白酶-12的表达增加，加入干扰素-γ中和免疫球蛋白可抑制其表达。人分泌性白细胞蛋白水解酶抑制物是由炎症部位的细胞合成和分泌的一种11.7 kDa的阳离子非糖基化抗蛋白酶。我们已经证明分泌性白细胞蛋白水解酶抑制剂可以抑制干扰素-γ诱导的巨噬细胞产生组织蛋白酶S。分泌性白细胞蛋白水解酶抑制物可抑制干扰素诱导的抑制物kappa Bβ的降解和核因子kappa B的活化，分泌性白细胞蛋白水解酶抑制物可能是慢性阻塞性肺疾病中潜在的蛋白水解酶抑制物。
We have demonstrated that bronchoalveolar lavage fluid from chronic obstructive pulmonary disease patients contains higher levels of interferon-gamma compared with controls. Interferon-gamma is a potent inducer of various cathepsins and matrix metalloproteases. Therefore, we postulated that interferon-gamma could induce protease expression by macrophages in acute and chronic lung disease. Chronic obstructive pulmonary disease patients had greater levels of cathepsin S and matrix metalloprotease-12 in their bronchoalveolar lavage fluid. Macrophages incubated with chronic obstructive pulmonary disease bronchoalveolar lavage fluid exhibited increased expression of cathepsin S and matrix metalloprotease-12, which was inhibited by the addition of interferon-gamma-neutralizing immunoglobulin. Human secretory leukocyte protease inhibitor is an 11.7-kDa cationic non-glycosylated antiprotease synthesized and secreted by cells at the site of inflammation. We have demonstrated that secretory leukocyte protease inhibitor can inhibit interferon-gamma-induced cathepsin S production by macrophages. Pretreatment of macrophages with secretory leukocyte protease inhibitor inhibited interferon-gamma-induced inhibitor kappa B beta degradation and activation of nuclear factor kappa B. Secretory leukocyte protease inhibitor may prove to be therapeutically important as a potential inhibitor of protease expression in chronic obstructive pulmonary disease.