Elafin prevents lipopolysaccharide-induced AP-1 and NF-κB activation via an effect on the ubiquitin-proteasome pathway
Elafin prevents lipopolysaccharide-induced AP-1 and NF-κB activation via an effect on the ubiquitin-proteasome pathway
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DOI：
10.1074/jbc.m604844200
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发表时间：
2006-11-17
影响因子：
4.8
通讯作者：
McElvaney, Noel G.
中科院分区：
文献类型：
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作者：
Butler, Marcus W.;Robertson, Ian;McElvaney, Noel G.
丝氨酸抗蛋白酶弹性蛋白酶由单核细胞、肺泡巨噬细胞、嗜中性粒细胞和粘膜表面表达，并具有抗微生物活性。还已知其通过尚未鉴定的机制减少脂多糖诱导的中性粒细胞流入鼠肺泡以及消除脂多糖诱导的基质金属蛋白酶9、巨噬细胞抑制蛋白2和肿瘤坏死因子-α的产生。在这份报告中，我们已经表明，弹力素抑制脂多糖诱导的单核细胞的单核细胞趋化蛋白-1的生产，通过抑制AP-1和NF-κ B激活。Elafin阻止脂多糖诱导的AP-1，c-Jun和JNK磷酸化，但对p38磷酸化没有影响。脂多糖诱导的IL-1 R相关激酶1、I κ B α和I κ B β降解被弹性蛋白酶抑制，但I κ B α磷酸化不受影响。多聚泛素化蛋白包括多聚泛素化I κ B α显示在弹力蛋白存在下积累。这些结果表明弹性蛋白酶抑制脂多糖诱导的AP-1和NF-κ B活化通过影响泛素-蛋白酶体途径发生。
The serine anti-protease elafin is expressed by monocytes, alveolar macrophages, neutrophils, and at mucosal surfaces and possesses antimicrobial activity. It is also known to reduce lipopolysaccharide-induced neutrophil influx into murine alveoli as well as to abrogate lipopolysaccharide-induced production of matrix metalloprotease 9, macrophage inhibitory protein 2, and tumor necrosis factor-alpha by as-yet unidentified mechanisms. In this report we have shown that elafin inhibits the lipopolysaccharide-induced production of monocyte chemoattractant protein-1 in monocytes by inhibiting AP-1 and NF-kappa B activation. Elafin prevented lipopolysaccharide-induced phosphorylation of AP-1, c-Jun, and JNK but had no effect on phosphorylation of p38. The lipopolysaccharide-induced degradation of IL-1R-associated kinase 1, I kappa B alpha, and I kappa B beta was inhibited by elafin but phosphorylation of I kappa B alpha was unaffected. Polyubiquitinated protein including polyubiquitinated I kappa B alpha was shown to accumulate in the presence of elafin. These results suggest that inhibition by elafin of lipopolysaccharide-induced AP-1 and NF-kappa B activation occurs via an effect on the ubiquitin-proteasome pathway.