N-AcetyI-L-cysteine and pyrrolidine dithiocarbamate inhibited nuclear factor-κB activation in alveolar macrophages by different mechanisms  

作　　者：Ya-qing LI Zhen-xiang ZHANGI Yong-jian XU Wang NI Shi-xin CHEN Zhao YANG Dan MA 

机构地区：[1]Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan430030, China

出　　处：《Acta Pharmacologica Sinica》2006年第3期339-346,共8页中国药理学报（英文版）

摘　　要：Aim： To study the effects of N-acetyl-L-cysteine （NAC） and pyrrolidine dithiocarbamate （PDTC） on the phosphorylation of IκB kinase （IKK）β, IKKα, and IκBα in alveolar macrophages （AM）, and to explore the pharmacological mechanisms of NAC and PDTC as inhibitors of NF-κB activation. Methods： AM were collected from bronchoalveolar lavage fluid from the patients with chronic obstructive pulmonary disease. The AM were incubated for 1.5 h with NAC and PDTC, and then stimulated for 90 min by either tumor necrosis factor （TNF）-α or interleukin （IL）-1. Western blotting was used to detect the protein phosphorylation levels of IKKβ, IKKa, and IκBα. NF-κB activity was analyzed by using an electrophoretic mobility shift assay. Results： NAC inhibited the phosphorylation of IKKβ, IKKα, and IKBα induced by TNF-α, but had no effect on the phosphorylation of IKKβ, IKKa and IκBα induced by IL-1. PDTC did not inhibit the phosphorylation of IκBα induced by TNF-α or IL-1. Similarly, NAC inhibited the activation of NF-κB induced by TNF-α, but had no effect on the activation of NF-κB induced by IL-1. PDTC significantly inhibited the activation of NF-κB induced by TNF-α and IL-1. The electrophoretic mobility shift assay also showed that PDTC and NAC do not directly inhibit NF-κB DNA binding activity in vitro. Conclusion： PDTC prevents the degradation of NF-κBα via the ubiquitylation-proteasome proteolytic pathway. NAC can inhibit the processes upstream of IKK activation induced by TNF-α, which results in the decline of NF-κB activity.Aim： To study the effects of N-acetyl-L-cysteine （NAC） and pyrrolidine dithiocarbamate （PDTC） on the phosphorylation of IκB kinase （IKK）β, IKKα, and IκBα in alveolar macrophages （AM）, and to explore the pharmacological mechanisms of NAC and PDTC as inhibitors of NF-κB activation. Methods： AM were collected from bronchoalveolar lavage fluid from the patients with chronic obstructive pulmonary disease. The AM were incubated for 1.5 h with NAC and PDTC, and then stimulated for 90 min by either tumor necrosis factor （TNF）-α or interleukin （IL）-1. Western blotting was used to detect the protein phosphorylation levels of IKKβ, IKKa, and IκBα. NF-κB activity was analyzed by using an electrophoretic mobility shift assay. Results： NAC inhibited the phosphorylation of IKKβ, IKKα, and IKBα induced by TNF-α, but had no effect on the phosphorylation of IKKβ, IKKa and IκBα induced by IL-1. PDTC did not inhibit the phosphorylation of IκBα induced by TNF-α or IL-1. Similarly, NAC inhibited the activation of NF-κB induced by TNF-α, but had no effect on the activation of NF-κB induced by IL-1. PDTC significantly inhibited the activation of NF-κB induced by TNF-α and IL-1. The electrophoretic mobility shift assay also showed that PDTC and NAC do not directly inhibit NF-κB DNA binding activity in vitro. Conclusion： PDTC prevents the degradation of NF-κBα via the ubiquitylation-proteasome proteolytic pathway. NAC can inhibit the processes upstream of IKK activation induced by TNF-α, which results in the decline of NF-κB activity.

关 键 词：NF-kappa B ACETYLCYSTEINE pyrrolidinedithiocarbamic acid alveolar macrophage 

分 类 号：R78[医药卫生—口腔医学]