Aim:To study the effects of N-acetyl-L-cysteine(NAC)and pyrrolidine dithio-carbamate(PDTC)on the phosphorylation of IκB kinase(IKK)β,IKKα,and IλBαin alveolar macrophages(AM),and to explore the pharmacological mechanisms ofNAC and PDTC as inhibitors of NF-κB activation.Methods:AM were collectedfrom bronchoalveolar lavage fluid from the patients with chronic obstructive pul-monary disease.The AM were incubated for 1.5 h with NAC and PDTC,and thenstimulated 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,IKKα,and IκBα.NF-κB activity was analyzed by using an electrophoretic mobil-ity shift assay.Results:NAC inhibited the phosphorylation of IKKβ,IKKα,andIκBα induced by TNF-α,but had no effect on the phosphorylation of IKKβ,IKKαand IκBα induced by IL-1.PDTC did not inhibit the phosphorylation of IκBαinduced by TNF-α or IL-1.Similarly,NAC inhibited the activation of NF-κBinduced 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 notdirectly inhibit NF-κB DNA binding activity in vitro.Conclusion:PDTC preventsthe degradation of IκBα 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 dithio-carbamate (PDTC) on the phosphorylation of IκB kinase (IKK) β, IKKα, and IλBαin 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 pulmonale disease. AM were incubated for 1.5 h with NAC and PDTC, and the 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, IKKα, and IκBα. NF-κB activity was analyzed by using an electrophoretic mobil-ity shift assay . Results: NAC inhibited the phosphorylation of IKKβ, IKKα, and IκBα induced by TNF-α, but had no effect on the phosphorylation of IKKβ, IKKαand IκBα induced by IL-1.PDTC did not inhibit the phosphorylation of IκBαinduced by TNF-α or IL-1.Similarly, NAC inhibited the activation of NF -κBinduced 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 assay that PDTC and NAC do not directly inhibit NF-κB DNA binding activity in vitro. Conclusion: PDTC prevent degradation of IκBα 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.